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Beneficial effect of low-level laser therapy in acute lung injury after i-I/R is dependent on the secretion of IL-10 and independent of the TLR/MyD88 signaling

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Abstract

The use of low-level laser for lung inflammation treatment has been evidenced in animal studies as well as clinical trials. The laser action mechanism seems to involve downregulation of neutrophil chemoattractants and transcription factors. Innate immune responses against microorganisms may be mediated by toll-like receptors (TLR). Intestinal ischemia and reperfusion (i-I/R) lead to bacterial product translocation, such as endotoxin, which consequently activates TLRs leading to intestinal and lung inflammation after gut trauma. Thus, the target of this study was to investigate the role of TLR activation in the laser (660 nm, 30 mW, 67.5 J/cm2, 0.375 mW/cm2, 5.4 J, 180 s, and spot size with 0.08 cm2) effect applied in contact with the skin on axillary lymph node in lung inflammation induced by i-I/R through a signaling adaptor protein known as myeloid differentiation factor 88 (MyD88). It is a quantitative, experimental, and laboratory research using the C57Bl/6 and MyD88−/− mice (n = 6 mice for experimental group). Statistical differences were evaluated by ANOVA and the Tukey-Kramer multiple comparisons test to determine differences among groups. In order to understand how the absence of MyD88 can interfere in the laser effect on lung inflammation, MyD88−/− mice were treated or not with laser and subjected to occlusion of the superior mesenteric artery (45 min) followed by intestinal reperfusion (4 h). In summary, the laser decreased the MPO activity and the lung vascular permeability, thickened the alveolar septa, reduced both the edema and the alveolar hemorrhage, as well as significantly decreased neutrophils infiltration in MyD88-deficient mice as well in wild-type mice. It noted a downregulation in chemokine IL-8 production as well as a cytokine IL-10 upregulation in these animals. The results also evidenced that in absence of IL-10, the laser effect is reversed. Based on these results, we suggest that the beneficial effect of laser in acute lung injury after i-I/R is dependent on the secretion of IL-10 and independent of the TLR/MyD88 signaling.

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References

  1. Sirotković-Skerlev M, Plestina S, Bilić I, Kovac Z (2006) Pathophysiology of ischaemia-reperfusion injury. Lijec Vjesn 128:87–95

    PubMed  Google Scholar 

  2. Halldorsson AO, Kronon MT, Allen BS, Rahman S, Wang T (2000) Lowering reperfusion pressure reduces the injury after pulmonary ischemia. Ann Thorac Surg 69:198–203

    Article  CAS  PubMed  Google Scholar 

  3. Souza DG, Soares AC, Pinho V, Torloni H, Reis LF, Teixeira MM, Dias AA (2002) Increased mortality and inflammation in tumor necrosis factor-stimulated gene-14 transgenic mice after ischemia and reperfusion injury. Am J Pathol 160:1755–1765

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Victoni T, Coelho FR, Soares AL, de Freitas A, Secher T, Guabiraba R, Erard F, de Oliveira-Filho RM, Vargaftig BB, Lauvaux G, Kamal MA, Ryffel B, Moser R, Tavares-de-Lima W (2010) Local and remote tissue injury upon intestinal ischemia and reperfusion depends on the TLR/MyD88 signaling pathwa. Med Microbiol Immunol 199:35–42

    Article  CAS  PubMed  Google Scholar 

  5. An S, Hishikawa Y, Liu J, Koji T (2007) Lung injury after ischemia-reperfusion of small intestine in rats involves apoptosis of type II alveolar epithelial cells mediated by TNF-alpha and activation of bid pathway. Apoptosis 12:1989–2001

    Article  CAS  PubMed  Google Scholar 

  6. Kiss J, Jalkanen S, Fülöp F, Savunen T, Salmi M (2008) Ischemiareperfusion injury is attenuated in VAP-1-deWcient mice and by VAP-1 inhibitors. Eur J Immunol 38:3041–3049

    Article  CAS  PubMed  Google Scholar 

  7. Kim BS, Lim SW, Li C, Kim JS, Sun BK, Ahn KO, Han SW, Kim J, Yang CW (2005) Ischemia-reperfusion injury activates innate immunity in rat kidneys. Transplantation 79:1370–1377

    Article  PubMed  Google Scholar 

  8. Jiang D, Liang J, Li Y, Noble PW (2006) The role of toll-like receptors in non-infectious lung injury. Cell Res 16:693–701

    Article  CAS  PubMed  Google Scholar 

  9. Iwasaki A, Medzhitov R (2004) Toll-like receptor control of the adaptive immune responses. Nat Immunol 5:987–995

    Article  CAS  PubMed  Google Scholar 

  10. Zhai Y, Shen XD, O’Connell R, Gao F, Lassman C, Busuttil RW, Cheng G, Kupiec-Weglinski JW (2004) Cutting edge: TLR4 activation mediates liver ischemia/reperfusion inflamatory response via IFN regulatory factor 3-dependent MyD88-independent pathway. J Immunol 173:7115–7119

    Article  CAS  PubMed  Google Scholar 

  11. Shigeoka AA, Holscher TD, King AJ, Hall FW, Kiosses WB, Tobias PS, Mackman N, McKay DB (2007) TLR2 is constitutively expressed within the kidney and participates in ischemic renal injury through both MyD88-dependent and -independent pathways. J Immunol 178:6252–6258

    Article  CAS  PubMed  Google Scholar 

  12. Trentin-Sonoda M, da Silva RC, Kmit FV, Abrahão MV, Monnerat Cahli G, Brasil GV, Muzi-Filho H, Silva PA, Tovar-Moll FF, Vieyra A, Medei E, Carneiro-Ramos MS (2015) Knockout of toll-like receptors 2 and 4 prevents renal ischemia-reperfusion-induced cardiac hypertrophy in mice. PLoS One 10(10):e0139350. doi:10.1371/journal.pone.0139350

    Article  PubMed  PubMed Central  Google Scholar 

  13. Chang WJ, Chen PH, Liu WC, Hsu CM (2008) TLR ligand decreases mesenteric ischemia and reperfusion injury-induced gut damage through TNF-alpha signaling. Shock 30:563–570

    Article  PubMed  Google Scholar 

  14. Yamamoto M, Takeda K, Akira S (2004) TIR domain—containing adaptors regulate TLR-mediated signaling pathways. Mol Immunol 40:861–868

    Article  CAS  PubMed  Google Scholar 

  15. Yamamoto M, Sato S, Hemmi H, Hoshino K, Kaisho T, Sanjo H, Takeuchi O, Sugiyama M, Okabe M, Takeda K, Akira S (2003) Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway. Science 301:640–643

    Article  CAS  PubMed  Google Scholar 

  16. Akira S, Uematsu S, Takeuchi O (2006) Pathogen recognition and innate immunity. Cell 124:783–801

    Article  CAS  PubMed  Google Scholar 

  17. Oshiumi H, Matsumoto M, Funami K, Akazawa T, Seya T (2003) TICAM-1, an adaptor molecule that participates in Toll-like receptor 3-mediated interferon-beta induction. Nat Immunol 4:161–167

    Article  CAS  PubMed  Google Scholar 

  18. Phelan P, Merry HE, Hwang B, Mulligan MS (2015) Differential toll-like receptor activation in lung ischemia reperfusion injury. J Thorac Cardiovasc Surg 149:1653–1661

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Altemeier WA, Liles WC, Villagra-Garcia A, Matute-Bello G, Glenny RW (2013) Ischemia-reperfusion lung injury is attenuated in MyD88-deficient mice. PLoS One 8, e77123

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Kawai T, Adachi O, Ogawa T, Takeda K, Akira S (1999) Unresponsiveness of MyD88-deficient mice to endotoxin. Immunity 11:115–122

    Article  CAS  PubMed  Google Scholar 

  21. Bjordal JM, Johnson MI, Iversen V, Aimbire F, Lopes-Martins RA (2006) Photoradiation in acute pain: a systematic review of possible mechanisms of action and clinical effects in randomized placebo-controlled trials. Photomed Laser Surg 24:158–168

    Article  CAS  PubMed  Google Scholar 

  22. Huang YY, Sharma SK, Carroll J, Hamblin MR (2011) Biphasic dose response in low level light therapy—an update. Dose Response 9:602–618

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Chow RT, Heller GZ, Barnsley L (2006) The effect of 300 mW, 830 nm laser on chronic neck pain: a double-blind, ranomized, placebo-controlled study. Pain 124:201–210

    Article  PubMed  Google Scholar 

  24. Chow RT, Johnson MI, Lopes-Martins RA, Bjordal JM (2009) Efficacy of low-level laser therapy in the management of neck pain: a systematic review and meta-analysis of randomised placebo or active-treatment controlled trials. Lancet 374:1897–1908

    Article  PubMed  Google Scholar 

  25. Xavier M, David DR, de Souza RA, Arrieiro AN, Miranda H, Santana ET, Silva JA Jr, Salgado MA, Aimbire F, Albertini R (2010) Anti-inflammatory effects of low-level light emitting diode therapy on Achilles tendinitis in rats. Lasers Surg Med 42:553–558

    Article  PubMed  Google Scholar 

  26. Kashanskaia EP, Fedorov AA (2009) Low-intensity laser radiation in the combined treatment of patients with chronic obstructive bronchitis. Vopr Kurortol Fizioter Lech Fiz Kult 2:19–22

    Google Scholar 

  27. Landyshev IS, Avdeeva NV, Goborov ND, Krasavina NP, Tikhonova GA, Tkacheva SI (2002) Efficacy of low intensity laser irradiation and sodium nedocromil in the complex treatment of patients with bronchial asthma. Ter Arkh 74:25–28

    PubMed  Google Scholar 

  28. de Lima FM, Vitoretti L, Coelho F, Albertini R, Breithaupt-Faloppa AC, de Lima WT, Aimbire F (2013) Suppressive effect of low-level laser therapy on tracheal hyperresponsiveness and lung inflammation in rat subjected to intestinal ischemia and reperfusion. Lasers Med Sci 28:551–564

    Article  PubMed  Google Scholar 

  29. de Lima FM, Albertini R, Dantas Y, Maia-Filho AL, Santana Cde L, Castro-Faria-Neto HC, França C, Villaverde AB, Aimbire F (2013) Low-level laser therapy restores the oxidative stress balance in acute lung injury induced by gut ischemia and reperfusion. Photochem Photobiol 89:179–188

    Article  PubMed  Google Scholar 

  30. Yamagishi Y, Horie Y, Kato S, Kajihara M, Tamai H, Granger DN, Ishii H (2002) Ethanol modulates gut ischemia/reperfusion-induced liver injury in rats. Am J Physiol Gastrointest Liver Physiol 282:G640–G646

    Article  CAS  PubMed  Google Scholar 

  31. De Lima FM, Aimbire F, Miranda H, Vieira RP, de Oliveira AP, Albertini R (2014) Low-level laser therapy attenuates the myeloperoxidase activity and inflammatory mediator generation in lung inflammation induced by gut ischemia and reperfusion: a dose-response study. J Lasers Med Sci 5:63–70

    PubMed  PubMed Central  Google Scholar 

  32. Soares AL, Coelho FR, Guabiraba R, Kamal M, Vargaftig BB, Li L, Li J, Tavares-de-Lima W, Ryffel B (2010) Tumor necrosis factor is not associated with intestinal ischemia/reperfusion-induced lung inflammation. Shock 34:306–313

    Article  CAS  PubMed  Google Scholar 

  33. Zanotti G, Casiraghi M, Abano JB, Tatreau JR, Sevala M, Berlin H, Smyth S, Funkhouser WK, Burridge K, Randell SH, Egan TM (2009) Novel critical role of toll-like receptor 4 in lung ischemia-reperfusion injury and edema. Am J Physiol Lung Cell Mol Physiol 297:52–63

    Article  Google Scholar 

  34. Matthay MA (1990) The adult respiratory distress syndrome: definition and prognosis. Clin Chest Med 11:575–580

    CAS  PubMed  Google Scholar 

  35. Matthay MA, Wiener-Kronish JP (1990) Intact epithelial barrier function is critical for the resolution of alveolar edema in humans. Am Rev Respir Dis 142:1250–1257

    Article  CAS  PubMed  Google Scholar 

  36. Van Soeren MH, Diehl-Jones WL, Maykut RJ, Haddara WM (2000) Pathophysiology and implications for treatment of acute respiratory distress syndrome. AACN Clin Issues 11:179–197

    Article  PubMed  Google Scholar 

  37. Desai SR (2002) Acute respiratory distress syndrome: imaging of the injured lung. Clin Radiol 57:8–17

    Article  PubMed  Google Scholar 

  38. Turner MD, Nedjai B, Hurst T, Pennington DJ (2014) Cytokines and chemokines: at the crossroads of cell signalling and inflammatory disease. Biochim Biophys Acta 1843:2563–2582

    Article  CAS  PubMed  Google Scholar 

  39. Miller EJ, Cohen AB, Nagao S, Griffith D, Maunder RJ, Martin TR, Weiner-Kronish JP, Sticherling M, Christophers E, Matthay MA (1992) Elevated levels of NAP-1/interleukin-8 are present in the airspaces of patients with the adult respiratory distress syndrome and are associated with increased mortality. Am Rev Respir Dis 146:427–432

    Article  CAS  PubMed  Google Scholar 

  40. Soranno DE, Rodell CB, Altmann C, Duplantis J, Andres-Hernando A, Burdick JA, Faubel S (2016) Delivery of interleukin-10 via injectable hydrogels improves renal outcomes and reduces systemic inflammation following ischemic acute kidney injury in mice. Am J Physiol Renal Physiol 311:362–372

    Article  Google Scholar 

  41. Miranda da Silva C, Peres Leal M, Brochetti RA, Braga T, Vitoretti LB, Saraiva Câmara NO, Damazo AS, Ligeiro-de-Oliveira AP, Chavantes MC, Lino-Dos-Santos-Franco A (2015) Low level laser therapy reduces the development of lung inflammation induced by formaldehyde exposure. PLoS One 10, e0142816

    Article  PubMed  PubMed Central  Google Scholar 

  42. Furuhashi T, Torii K, Kato H, Nishida E, Saito C, Morita A (2011) Efficacy of excimer light therapy (308nm) for palmoplantar pustulosis with the induction of circulating regulatory T cells. Exp Dermatol 20:768–770

    Article  CAS  PubMed  Google Scholar 

  43. Powell MJ, Thompson SA, Tone Y, Waldmann H, Tone M (2000) Posttranscriptional regulation of IL-10 gene expression through sequences in the 3′-untranslated region. J Immunol 165:292–296

    Article  CAS  PubMed  Google Scholar 

  44. Ma W, Lim W, Gee K, Aucoin S, Nandan D, Kozlowski M, Diaz-Mitoma F, Kumar A (2001) The p38 mitogen-activated kinase pathway regulates the human interleukin-10 promoter via the activation of Sp1 transcription factor in lipopolysaccharide-stimulated human macrophages. J Biol Chem 276:13664–13674

    CAS  PubMed  Google Scholar 

  45. Hofmann SR, Kubasch AS, Ioannidis C, Rösen-Wolff A, Girschick HJ, Morbach H, Hedrich CM (2015) Altered expression of IL-10 family cytokines in monocytes from CRMO patients result in enhanced IL-1β expression and release. Clin Immunol 161:300–307

    Article  CAS  PubMed  Google Scholar 

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Correspondence to F. Aimbire.

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Disclosure of potential conflicts of interest

Research funder: Research Support Foundation of São Paulo State (FAPESP); Grant number: 2008/08838/5. There is no conflict of interest with FAPESP.

Role of funding source

The FAPESP is an agency of the state of São Paulo that finances research projects with buying from equipment and reagents needed for research. In this manuscript, the role of funding source was finance purchases of MyD88 knockout animals and reagents for other experimental studies.

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The animals’ housing and use were in accordance with the guidelines of the Committee on Care and Use of Laboratory Animal Resources of the University of São Paulo, Institute of Biomedical Sciences, which are similar to the guidelines of the Canadian Council of Animal Care.

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The experiments were done with mice.

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Carvalho, J.L., Britto, A., de Oliveira, A.P.L. et al. Beneficial effect of low-level laser therapy in acute lung injury after i-I/R is dependent on the secretion of IL-10 and independent of the TLR/MyD88 signaling. Lasers Med Sci 32, 305–315 (2017). https://doi.org/10.1007/s10103-016-2115-4

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