Skip to main content
SpringerLink
Log in

Epithelial Dysfunction in Lung Diseases: Effects of Amino Acids and Potential Mechanisms

  • Chapter
  • First Online:
Amino Acids in Nutrition and Health

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1265))

Abstract

Lung diseases affect millions of individuals all over the world. Various environmental factors, such as toxins, chemical pollutants, detergents, viruses, bacteria, microbial dysbiosis, and allergens, contribute to the development of respiratory disorders. Exposure to these factors activates stress responses in host cells and disrupt lung homeostasis, therefore leading to dysfunctional epithelial barriers. Despite significant advances in therapeutic treatments for lung diseases in the last two decades, novel interventional targets are imperative, considering the side effects and limited efficacy in patients treated with currently available drugs. Nutrients, such as amino acids (e.g., arginine, glutamine, glycine, proline, taurine, and tryptophan), peptides, and bioactive molecules, have attracted more and more attention due to their abilities to reduce oxidative stress, inhibit apoptosis, and regulate immune responses, thereby improving epithelial barriers. In this review, we summarize recent advances in amino acid metabolism in the lungs, as well as multifaceted functions of amino acids in attenuating inflammatory lung diseases based on data from studies with both human patients and animal models. The underlying mechanisms for the effects of physiological amino acids are likely complex and involve cell signaling, gene expression, and anti-oxidative reactions. The beneficial effects of amino acids are expected to improve the respiratory health and well-being of humans and other animals. Because viruses (e.g., coronavirus) and environmental pollutants (e.g., PM2.5 particles) induce severe damage to the lungs, it is important to determine whether dietary supplementation or intravenous administration of individual functional amino acids (e.g., arginine-HCl, citrulline, N-acetylcysteine, glutamine, glycine, proline and tryptophan) or their combinations to affected subjects may alleviate injury and dysfunction in this vital organ.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

CaMKK2:

calcium/calmodulin-dependent kinase 2

COPD:

chronic obstructive pulmonary disease

IL-6:

interleukin 6

Keap1:

Kelch-like ECH associated protein 1

LPS:

lipopolysaccharide

NF-κB:

nuclear factor kappa B

NLR:

Nod-like receptors

NO:

nitric oxide

Nrf2:

nuclear factor erythroid 2-related factor

PAR:

protease-activated receptors

PRRs:

pathogen recognition receptors

RLR:

RIG-I-like receptors

ROS:

reactive oxygen species

Th:

T helper

TJs:

tight junctions

TLR:

Toll-like receptors

TNF-α:

tumor necrosis factor alpha

ZO:

zonulae occludens

References

  • Agostinelli E (2020) Biochemical and pathophysiological properties of polyamines. Amino Acids 52: 111–117

    Google Scholar 

  • Agusti A, Hogg JC (2019) Update on the pathogenesis of chronic obstructive pulmonary disease. N Engl J Med 381:1248–1256

    Article  CAS  PubMed  Google Scholar 

  • Amelio I, Cutruzzolá F, Antonov A, Agostini M, Melino G (2014) Serine and glycine metabolism in cancer. Trends Biochem Sci 39:191–198

    Google Scholar 

  • Atto B, Eapen MS, Sharma P, Frey U, Ammit AJ, Markos J, Chia C, Larby J, Haug G et al (2019) New therapeutic targets for the prevention of infectious acute exacerbations of COPD: role of epithelial adhesion molecules and inflammatory pathways. Clin Sci (Lond) 133:1663–1703

    Article  CAS  Google Scholar 

  • Berggren M, Dawson J, Moldeus P (1984) Glutathione biosynthesis in the isolated perfused rat lung: utilization of extracellular glutathione. FEBS Lett 176:189–192

    Article  CAS  PubMed  Google Scholar 

  • Boskabadi J, Mokhtari-Zaer A, Abareshi A, Khazdair MR, Emami B, Mohammadian Roshan N, Hosseini M, Boskabady MH (2018) The effect of captopril on lipopolysaccharide-induced lung inflammation. Exp Lung Res 44:191–200

    Article  CAS  PubMed  Google Scholar 

  • Bream-Rouwenhorst HR, Beltz EA, Ross MB, Moores KG (2008) Recent developments in the management of acute respiratory distress syndrome in adults. Am J Health Syst Pharm 65:29–36

    Article  CAS  PubMed  Google Scholar 

  • Budden KF, Gellatly SL, Wood DL, Cooper MA, Morrison M, Hugenholtz P, Hansbro PM (2017) Emerging pathogenic links between microbiota and the gut-lung axis. Nat Rev Microbiol 15:55–63

    Article  CAS  PubMed  Google Scholar 

  • Chao YK, Wu YC, Yang KJ, Chiang LL, Liu HP, Lin PJ, Chu Y (2011) Pulmonary perfusion with L-arginine ameliorates post-cardiopulmonary bypass lung injury in a rabbit model. J Surg Res 167:e77–e83

    Article  CAS  PubMed  Google Scholar 

  • Chen H, Ding Y, Chen W, Feng Y, Shi G (2019) Glibenclamide alleviates inflammation in oleic acid model of acute lung injury through NLRP3 inflammasome signaling pathway. Drug Des Devel Ther 13:1545–1554

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cho HY, Kleeberger SR (2020) Mitochondrial biology in airway pathogenesis and the role of NRF2. Arch Pharm Res 43:297–320

    Google Scholar 

  • Chu SJ, Lee TY, Yan HC, Lin SH, Li MH (2005) L-arginine prevents air embolism-induced acute lung injury in rats. Crit Care Med 33:2056–2060

    Article  CAS  PubMed  Google Scholar 

  • Curis E, Nicolis I, Moinard C, Osowska S, Zerrouk N, Benazeth S, Cynober L (2005) Almost all about citrulline in mammals. Amino Acids 29:177–205

    Article  CAS  PubMed  Google Scholar 

  • Dai ZL, Wu G, Zhu WY (2011) Amino acid metabolism in intestinal bacteria: links between gut ecology and host health. Front Biosci (Landmark Ed) 16:1768–1786

    Article  CAS  Google Scholar 

  • Dai ZL, Li XL, Xi PB, Zhang J, Wu G, Zhu WY (2012a) Metabolism of select amino acids in bacteria from the pig small intestine. Amino Acids 42:1597–1608

    Article  CAS  PubMed  Google Scholar 

  • Dai ZL, Li XL, Xi PB, Zhang J, Wu G, Zhu WY (2012b) Regulatory role for L-arginine in the utilization of amino acids by pig small-intestinal bacteria. Amino Acids 43:233–244

    Article  CAS  PubMed  Google Scholar 

  • Dai ZL, Li XL, Xi PB, Zhang J, Wu G, Zhu WY (2013) L-glutamine regulates amino acid utilization by intestinal bacteria. Amino Acids 45:501–512

    Article  CAS  PubMed  Google Scholar 

  • de Oliveira GP et al (2019) Glutamine therapy reduces inflammation and extracellular trap release in experimental acute respiratory distress syndrome of pulmonary origin. Nutrients 11(4):831

    Article  PubMed Central  CAS  Google Scholar 

  • Dickson RP, Erb-Downward JR, Huffnagle GB (2013) The role of the bacterial microbiome in lung disease. Expert Rev Respir Med 7:245–257

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fan X, Li S, Wu Z, Dai Z, Li J, Wang X, Wu G (2019) Glycine supplementation to breast-fed piglets attenuates post-weaning jejunal epithelial apoptosis: a functional role of CHOP signaling. Amino Acids 51:463–473

    Article  CAS  PubMed  Google Scholar 

  • Faner R, Sibila O, Agusti A, Bernasconi E, Chalmers JD, Huffnagle GB, Manichanh C, Molyneaux PL, Paredes R et al (2017) The microbiome in respiratory medicine: current challenges and future perspectives. Eur Respir J 49(4):1602086

    Article  PubMed  Google Scholar 

  • Fukumoto J, Fukumoto I, Parthasarathy PT, Cox R, Huynh B, Ramanathan GK, Venugopal RB, Allen-Gipson DS, Lockey RF et al (2013) NLRP3 deletion protects from hyperoxia-induced acute lung injury. Am J Phys 305:C182–C189

    Article  CAS  Google Scholar 

  • Folkerts G, Kloek J, Muijsers RB, Nijkamp FP (2001) Reactive nitrogen and oxygen species in airway inflammation. Eur J Pharmacol 429:251–262

    Google Scholar 

  • Georas SN, Rezaee F (2014) Epithelial barrier function: at the front line of asthma immunology and allergic airway inflammation. J Allergy Clin Immunol 134:509–520

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grainge C, Rice P (2010) Management of phosgene-induced acute lung injury. Clin Toxicol (Phila) 48:497–508

    Article  CAS  Google Scholar 

  • Grisafi D, Tassone E, Dedja A, Oselladore B, Masola V, Guzzardo V, Porzionato A, Salmaso R, Albertin G et al (2012) L-citrulline prevents alveolar and vascular derangement in a rat model of moderate hyperoxia-induced lung injury. Lung 190:419–430

    Article  CAS  PubMed  Google Scholar 

  • Guo RF, Ward PA (2007) Role of oxidants in lung injury during sepsis. Antioxid Redox Signal 9:1991–2002

    Article  CAS  PubMed  Google Scholar 

  • Hamanaka RB, O’Leary EM, Witt LJ, Tian Y, Gokalp GA, Meliton AY, Dulin NO, Mutlu GM (2019) Glutamine metabolism is required for collagen protein synthesis in lung fibroblasts. Am J Respir Cell Mol Biol 61:597–606

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hartl D, Tirouvanziam R, Laval J, Greene CM, Habiel D, Sharma L, Yildirim AO, Dela Cruz CS, Hogaboam CM (2018) Innate immunity of the lung: from basic mechanisms to translational medicine. J Innate Immun 10:487–501

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • He Y, Wen Q, Yao F, Xu D, Huang Y, Wang J (2017) Gut-lung axis: the microbial contributions and clinical implications. Crit Rev Microbiol 43:81–95

    Article  CAS  PubMed  Google Scholar 

  • Herold S, Becker C, Ridge KM, Budinger GR (2015) Influenza virus-induced lung injury: pathogenesis and implications for treatment. Eur Respir J 45:1463–1478

    Google Scholar 

  • He Y, Fan X, Liu N, Song Q, Kou J, Shi Y, Luo X, Dai Z, Yang Y et al (2019) L-glutamine represses the unfolded protein response in the small intestine of weanling piglets. J Nutr 149:1904–1910

    Article  PubMed  Google Scholar 

  • Hoet PH, Nemery B (2000) Polyamines in the lung: polyamine uptake and polyamine-linked pathological or toxicological conditions. Am J Physiol Lung Cell Mol Physiol 278:L417–433

    Google Scholar 

  • Hou Y, Wu G (2017) Nutritionally nonessential amino acids: a misnomer in nutritional sciences. Adv Nutr 8:137–139

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hou Y, Yin Y, Wu G (2015) Dietary essentiality of “nutritionally non-essential amino acids” for animals and humans. Exp Biol Med (Maywood) 240:997–1007

    Article  CAS  Google Scholar 

  • Hou YQ, He WL, Hu SD, Wu G (2019) Composition of polyamines and amino acids in plant-source foods for human consumption. Amino Acids 51:1153–1165

    Google Scholar 

  • Inoue S, Ikeda H (2019) Differences in plasma amino acid levels in patients with and without bacterial infection during the early stage of acute exacerbation of COPD. Int J Chron Obstruct Pulmon Dis 14:575–583

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jiao N, Wu Z, Ji Y, Wang B, Dai Z, Wu G (2015) L-glutamate enhances barrier and antioxidative functions in intestinal porcine epithelial cells. J Nutr 145:2258–2264

    Article  CAS  PubMed  Google Scholar 

  • Kanai Y, Hediger MA (1992) Primary structure and functional characterization of a high-affinity glutamate transporter. Nature 360:467–471

    Article  CAS  PubMed  Google Scholar 

  • Kandasamy P, Gyimesi G, Kanai Y, Hediger MA (2018) Amino acid transporters revisited: new views in health and disease. Trends Biochem Sci 43:752–789

    Article  CAS  PubMed  Google Scholar 

  • Kosmider B, Messier EM, Chu HW, Mason RJ (2011) Human alveolar epithelial cell injury induced by cigarette smoke. PLoS One 6:e26059

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kouis P, Hadjisavvas A, Middleton N, Papatheodorou SI, Kyriacou K, Yiallouros PK (2018) The effect of L-arginine on ciliary beat frequency in PCD patients, non-PCD respiratory patients and healthy controls. Pulm Pharmacol Ther 48:15–21

    Article  CAS  PubMed  Google Scholar 

  • Lai CC, Liu WL, Chen CM (2014) Glutamine attenuates acute lung injury caused by acid aspiration. Nutrients 6:3101–3116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lambrecht BN, Hammad H (2014) Allergens and the airway epithelium response: gateway to allergic sensitization. J Allergy Clin Immunol 134:499–507

    Article  CAS  PubMed  Google Scholar 

  • Lang JD, McArdle PJ, O’Reilly PJ, Matalon S (2002) Oxidant-antioxidant balance in acute lung injury. Chest 122:314S–320S

    Article  CAS  PubMed  Google Scholar 

  • Lee S, Nakahira K, Dalli J, Siempos II, Norris PC, Colas RA, Moon JS, Shinohara M, Hisata S et al (2017) NLRP3 inflammasome deficiency protects against microbial sepsis via increased lipoxin B4 synthesis. Am J Respir Crit Care Med 196:713–726

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li YJ, Shimizu T, Shinkai Y, Hirata Y, Inagaki H, Takeda K, Azuma A, Yamamoto M, Kawada T (2017) Nrf2 regulates the risk of a diesel exhaust inhalation-induced immune response during bleomycin lung injury and fibrosis in mice. Int J Mol Sci 18:649

    Article  PubMed Central  CAS  Google Scholar 

  • Li P, Wu G (2018) Roles of dietary glycine, proline and hydroxyproline in collagen synthesis and animal growth. Amino Acids 50:29–38

    Google Scholar 

  • Li P, Wu G (2020) Composition of amino acids and related nitrogenous nutrients in feedstuffs for animal diets. Amino Acids 52:523–542

    Google Scholar 

  • Liang HW, Dai ZL, Kou J, Sun KJ, Chen JQ, Yang Y, Wu G, Wu ZL (2019) Dietary l-tryptophan supplementation enhances the intestinal mucosal barrier function in weaned piglets: Implication of tryptophan-metabolizing microbiota. Int J Mol Sci 20:20

    Google Scholar 

  • Liu N, Ma X, Luo X, Zhang Y, He Y, Dai Z, Yang Y, Wu G, Wu Z (2018) L-Glutamine attenuates apoptosis in porcine enterocytes by regulating glutathione-related redox homeostasis. J Nutr 148:526–534

    Article  PubMed  Google Scholar 

  • Liu H, Gu C, Liu M, Liu G, Wang D, Liu X, Wang Y (2019) Ventilator-induced lung injury is alleviated by inhibiting NLRP3 inflammasome activation. Mol Immunol 111:1–10

    Article  CAS  PubMed  Google Scholar 

  • Lukaszewicz G, Abcouwer SF, Labow BI, Souba WW (1997) Glutamine synthetase gene expression in the lungs of endotoxin-treated and adrenalectomized rats. Am J Phys 273:L1182–L1190

    CAS  Google Scholar 

  • Ma X, Zhang Y, Jiang D, Yang Y, Wu G, Wu Z (2019) Protective effects of functional amino acids on apoptosis, inflammatory response, and pulmonary fibrosis in lipopolysaccharide-challenged mice. J Agric Food Chem 67:4915–4922

    Article  CAS  PubMed  Google Scholar 

  • Mabalirajan U, Ahmad T, Leishangthem GD, Dinda AK, Agrawal A, Ghosh B (2010) L-Arginine reduces mitochondrial dysfunction and airway injury in murine allergic airway inflammation. Int Immunopharmacol 10:1514–1519

    Article  CAS  PubMed  Google Scholar 

  • Marudamuthu AS, Bhandary YP, Fan L, Radhakrishnan V, MacKenzie B, Maier E, Shetty SK, Nagaraja MR et al (2019) Caveolin-1-derived peptide limits development of pulmonary fibrosis. Sci Transl Med 11:eaat2848

    Article  CAS  PubMed  Google Scholar 

  • Mattila P, Joenvaara S, Renkonen J, Toppila-Salmi S, Renkonen R (2011) Allergy as an epithelial barrier disease. Clin Transl Allergy 1:5

    Article  PubMed  PubMed Central  Google Scholar 

  • McGee MM, Greengard O, Knox WE (1972) The quantitative determination of phenylalanine hydroxylase in rat tissues. Its developmental formation in liver. Biochem J 127:669–674

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McNeal CJ, Meininger CJ, Wilborn CD, Tekwe CD, Wu G (2018) Safety of dietary supplementation with arginine in adult humans. Amino Acids 50:1215–1229

    Google Scholar 

  • Michaeloudes C, Bhavsar PK, Mumby S, Xu B, Hui CKM, Chung KF, Adcock IM (2019) Role of metabolic reprogramming in pulmonary innate immunity and its impact on lung diseases. J Innate Immun 12:1–16

    Google Scholar 

  • Mizumura K, Maruoka S, Shimizu T, Gon Y (2020) Role of Nrf2 in the pathogenesis of respiratory diseases. Respir Investig 58:28–35

    Article  PubMed  Google Scholar 

  • Murakami K, Enkhbaatar P, Yu YM, Traber LD, Cox RA, Hawkins HK, Tompkins RG, Herndon D, Traber DL (2007) L-arginine attenuates acute lung injury after smoke inhalation and burn injury in sheep. Shock 28:477–483

    Article  CAS  PubMed  Google Scholar 

  • Nakaya M, Xiao Y, Zhou X, Chang JH, Chang M, Cheng X, Blonska M, Lin X, Sun SC (2014) Inflammatory T cell responses rely on amino acid transporter ASCT2 facilitation of glutamine uptake and mTORC1 kinase activation. Immunity 40:692–705

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nalysnyk L, Cid-Ruzafa J, Rotella P, Esser D (2012) Incidence and prevalence of idiopathic pulmonary fibrosis: review of the literature. Eur Respir Rev 21:355–361

    Article  PubMed  Google Scholar 

  • Nieweld C, Summer R (2019) Activated fibroblasts: gluttonous for glutamine. Am J Respir Cell Mol Biol 61:554–555

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • O’Dwyer DN, Dickson RP, Moore BB (2016) The lung microbiome, immunity and the pathogenesis of chronic lung disease. J Immunol 196:4839–4847 

    Google Scholar 

  • Ogata-Suetsugu S, Yanagihara T, Hamada N, Ikeda-Harada C, Yokoyama T, Suzuki K, Kawaguchi T, Maeyama T, Kuwano K et al (2017) Amphiregulin suppresses epithelial cell apoptosis in lipopolysaccharide-induced lung injury in mice. Biochem Biophys Res Commun 484:422–428

    Article  CAS  PubMed  Google Scholar 

  • Oudemans-van Straaten HM, Bosman RJ, Treskes M, van der Spoel HJ, Zandstra DF (2001) Plasma glutamine depletion and patient outcome in acute ICU admissions. Intensive Care Med 27:84–90

    Article  CAS  PubMed  Google Scholar 

  • Price ME, Sisson JH (2019) Redox regulation of motile cilia in airway disease. Redox Biol 27:101146

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Qian M et al (2018) PICK1 deficiency exacerbates sepsis-associated acute lung injury and impairs glutathione synthesis via reduction of xCT. Free Radic Biol Med 118:23–34

    Article  CAS  PubMed  Google Scholar 

  • Rahman I, Biswas SK, Jimenez LA, Torres M, Forman HJ (2005) Glutathione, stress responses, and redox signaling in lung inflammation. Antioxid Redox Signal 7:42–59

    Article  CAS  PubMed  Google Scholar 

  • Remot A, Descamps D, Noordine ML, Boukadiri A, Mathieu E, Robert V, Riffault S, Lambrecht B, Langella P et al (2017) Bacteria isolated from lung modulate asthma susceptibility in mice. ISME J 11:1061–1074

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Segal LN, Rom WN, Weiden MD (2014) Lung microbiome for clinicians. New discoveries about bugs in healthy and diseased lungs. Ann Am Thorac Soc 11:108–116

    Article  PubMed  PubMed Central  Google Scholar 

  • Shi H, Han X, Jiang N, Cao Y, Alwalid O, Gu J (2020) Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study. Lancet Infect Dis 20:P425–434

    Google Scholar 

  • Souba WW, Herskowitz K, Plumley DA (1990) Lung glutamine metabolism. J Parenter Enter Nutr 14:68S–70S

    Article  CAS  Google Scholar 

  • Steelant B (2020) Epithelial dysfunction in chronic respiratory diseases, a shared endotype? Curr Opin Pulm Med 26:20–26

    Article  CAS  PubMed  Google Scholar 

  • Sugita K, Steer CA, Martinez-Gonzalez I, Altunbulakli C, Morita H, Castro-Giner F, Kubo T, Wawrzyniak P, Ruckert B et al (2018) Type 2 innate lymphoid cells disrupt bronchial epithelial barrier integrity by targeting tight junctions through IL-13 in asthmatic patients. J Allergy Clin Immunol 141:300–310

    Article  CAS  PubMed  Google Scholar 

  • Sze MA, Tsuruta M, Yang SW, Oh Y, Man SF, Hogg JC, Sin DD (2014) Changes in the bacterial microbiota in gut, blood, and lungs following acute LPS instillation into mice lungs. PLoS One 9:e111228

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Tatsuta M, Kan OK, Ishii Y, Yamamoto N, Ogawa T, Fukuyama S, Ogawa A, Fujita A, Nakanishi Y et al (2019) Effects of cigarette smoke on barrier function and tight junction proteins in the bronchial epithelium: protective role of cathelicidin LL-37. Respir Res 20:251

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Thimmulappa RK, Scollick C, Traore K, Yates M, Trush MA, Liby KT, Sporn MB, Yamamoto M, Kensler TW et al (2006) Nrf2-dependent protection from LPS induced inflammatory response and mortality by CDDO-Imidazolide. Biochem Biophys Res Commun 351:883–889

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Venoji R, Amirtharaj GJ, Kini A, Vanaparthi S, Venkatraman A, Ramachandran A (2015) Enteral glutamine differentially regulates Nrf 2 along the villus-crypt axis of the intestine to enhance glutathione levels. J Gastroenterol Hepatol 30:1740–1747

    Article  CAS  PubMed  Google Scholar 

  • Vigeland CL, Beggs HS, Collins SL, Chan-Li Y, Powell JD, Doerschuk CM, Horton MR (2019) Inhibition of glutamine metabolism accelerates resolution of acute lung injury. Physiol Rep 7:e14019

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wang W, Wu Z, Lin G, Hu S, Wang B, Dai Z, Wu G (2014) Glycine stimulates protein synthesis and inhibits oxidative stress in pig small intestinal epithelial cells. J Nutr 144:1540–1548

    Article  CAS  PubMed  Google Scholar 

  • Wang B, Wu G, Zhou Z, Dai Z, Sun Y, Ji Y, Li W, Wang W, Liu C, Han F, Wu Z (2015a) Glutamine and intestinal barrier function. Amino Acids 47:2143–2154

    Article  CAS  PubMed  Google Scholar 

  • Wang H, Zhang C, Wu G, Sun Y, Wang B, He B, Dai Z, Wu Z (2015b) Glutamine enhances tight junction protein expression and modulates corticotropin-releasing factor signaling in the jejunum of weanling piglets. J Nutr 145:25–31

    Article  CAS  PubMed  Google Scholar 

  • Wang B, Wu Z, Ji Y, Sun K, Dai Z, Wu G (2016) L-glutamine enhances tight junction integrity by activating CaMK kinase 2-AMP-activated protein kinase signaling in intestinal porcine epithelial cells. J Nutr 146:501–508

    Article  CAS  PubMed  Google Scholar 

  • Wang M, Tan G, Eljaszewicz A, Meng Y, Wawrzyniak P, Acharya S, Altunbulakli C, Westermann P, Dreher A et al (2019) Laundry detergents and detergent residue after rinsing directly disrupt tight junction barrier integrity in human bronchial epithelial cells. J Allergy Clin Immunol 143:1892–1903

    Article  CAS  PubMed  Google Scholar 

  • Wang B, Sun SQ, Liu MY, Chen H, Liu N, Wu ZL, Wu G, Dai ZL (2020) Dietary L-tryptophan supplementation regulates colonic serotonin homeostasis and inhibits gut inflammation in mice with dextran sodium sulfate-induced colitis. J Nutr 150:1966–1976

    Google Scholar 

  • Warheit-Niemi HI, Hult EM, Moore BB (2019) A pathologic two-way street: how innate immunity impacts lung fibrosis and fibrosis impacts lung immunity. Clin Transl Immunol 8:e1065

    Article  Google Scholar 

  • Wieczfinska J, Sokolowska M, Pawliczak R (2015) NOX modifiers-just a step away from application in the therapy of airway inflammation? Antioxid Redox Signal 23:428–445

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wilmore DW, Shabert JK (1998) Role of glutamine in immunologic responses. Nutrition 14:618–626

    Article  CAS  PubMed  Google Scholar 

  • Wu G (2013) Amino acids: biochemistry and nutrition. CRC Press, Boca Raton

    Book  Google Scholar 

  • Wu G (2014) Dietary requirements of synthesizable amino acids by animals: a paradigm shift in protein nutrition. J Anim Sci Biotechnol 5:34

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wu G (2020) Management of metabolic disorders (including metabolic diseases) in ruminant and nonruminant animals. In: Bazer FW, Lamb GC, Wu G (eds) Animal agriculture: challenges, innovations, and sustainability. Elsevier, New York, pp 471–492

    Google Scholar 

  • Wu G, Morris SM Jr (1998) Arginine metabolism: nitric oxide and beyond. Biochem J 336:1–17

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu BG, Segal LN (2017) Lung microbiota and its impact on the mucosal immune phenotype. Microbiol Spectr 5:BAD-0005-2016

    Google Scholar 

  • Wu G, Davis PK, Flynn NE, Knabe DA, Davidson JT (1997) Endogenous synthesis of arginine plays an important role in maintaining arginine homeostasis in postweaning growing pigs. J. Nutr 127:2342–2349

    Google Scholar 

  • Wu G, Meininger CJ, Knabe DA, Bazer FW, Rhoads JM (2000) Arginine nutrition in development, health and disease. Curr Opin Clin Nutr Metab Care 3:59–66

    Google Scholar 

  • Wu G, Bazer FW, Dai Z, Li D, Wang J, Wu Z (2014) Amino acid nutrition in animals: protein synthesis and beyond. Annu Rev Anim Biosci 2:387–417

    Article  CAS  PubMed  Google Scholar 

  • Wu G, Cross HR, Gehring KB, Savell JW, Arnold AN, McNeill SH (2016) Composition of free and peptide-bound amino acids in beef chuck, loin, and round cuts. J Anim Sci 94:2603–2613

    Google Scholar 

  • Wu G, Brown J, Zamora ML, Miller A, Satterfield MC, Meininger CJ, Steinhauser CB, Johnson GA, Burghardt RC, Bazer FW, Li Y, Johnson NM, Molina MJ, Zhang R (2019) Adverse organogenesis and predisposed long-term metabolic syndrome from prenatal exposure to fine particulate matter. Proc Natl Acad Sci USA 116:11590–11595

    Google Scholar 

  • Xu Y, Meng C, Liu G, Yang D, Fu L, Zhang M, Zhang Z, Xia H, Yao S et al (2016) Classically activated macrophages protect against lipopolysaccharide-induced acute lung injury by expressing amphiregulin in mice. Anesthesiology 124:1086–1099

    Article  CAS  PubMed  Google Scholar 

  • Xu F, Wen Z, Shi X, Fan J (2018) Inflammasome in the pathogenesis of pulmonary diseases. Exp Suppl 108:111–151

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yoshida K, Yoshimura K, Haniuda M (1999) L-arginine inhibits ischemia-reperfusion lung injury in rabbits. J Surg Res 85:9–16

    Article  CAS  PubMed  Google Scholar 

  • Zhang YL, Li QQ, Guo W, Huang Y, Yang J (2007) Effects of chronic ethanol ingestion on tight junction proteins and barrier function of alveolar epithelium in the rat. Shock 28:245–252

    Article  CAS  PubMed  Google Scholar 

  • Zhang H, Wang Z, Liu R, Qian T, Liu J, Wang L, Chu Y (2018) Reactive oxygen species stimulated pulmonary epithelial cells mediate the alveolar recruitment of FasL(+) killer B cells in LPS-induced acute lung injuries. J Leukoc Biol 104:1187–1198

    Article  CAS  PubMed  Google Scholar 

  • Zhang YC, Ma X, Jiang D, Chen JQ, Jia H, Wu ZL, Kim IH, Yang Y (2020) Glycine attenuates lipopolysaccharide-induced acute lung injury by regulating NLRP3 inflammasome and NRF2 signaling. Nutrients 12(3):611

    Google Scholar 

Download references

Acknowledgments

This work was supported by the National Natural Science Foundation of China (No. 31572423, and 31625025), the “111” Project (B16044), Jinxinnong Animal Science Development Foundation, and Texas A&M AgriLife Research (H-8200). Y.Y. and G.W. designed the review; J.C., Y. J., Y.Y., Z.W., and G.W. drafted the manuscript; Z.W., Y. Y., and G.W. revised and finalized the manuscript. Y.Y. and G.W. had primary responsibility for final content. All authors read and approved the final manuscript.

Author information

Authors and Affiliations

  1. State Key Laboratory of Animal Nutrition, China Agricultural University, Beijing, China

    Jingqing Chen, Yuhang Jin, Ying Yang & Zhenlong Wu

  2. Department of Animal Science, Texas A&M University, College Station, TX, USA

    Guoyao Wu

Authors
  1. Jingqing Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yuhang Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ying Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zhenlong Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Guoyao Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Animal Science, Texas A&M University, College Station, TX, USA

    Guoyao Wu

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Chen, J., Jin, Y., Yang, Y., Wu, Z., Wu, G. (2020). Epithelial Dysfunction in Lung Diseases: Effects of Amino Acids and Potential Mechanisms. In: Wu, G. (eds) Amino Acids in Nutrition and Health. Advances in Experimental Medicine and Biology, vol 1265. Springer, Cham. https://doi.org/10.1007/978-3-030-45328-2_4

Download citation

Publish with us

Policies and ethics

Search

Navigation