Abstract
The aim of this work was to investigate if the low-level laser therapy (LLLT) on acute lung inflammation (ALI) induced by lipopolysaccharide (LPS) is linked to tumor necrosis factor (TNF) in alveolar macrophages (AM) from bronchoalveolar lavage fluid (BALF) of mice. LLLT has been reported to actuate positively for relieving the late and early symptoms of airway and lung inflammation. It is not known if the increased TNF mRNA expression and dysfunction of cAMP generation observed in ALI can be influenced by LLLT. For in vivo studies, Balb/c mice (n = 5 for group) received LPS inhalation or TNF intra nasal instillation and 3 h after LPS or TNF-α, leukocytes in BALF were analyzed. LLLT administered perpendicularly to a point in the middle of the dissected bronchi with a wavelength of 660 nm and a dose of 4.5 J/cm2. The mice were irradiated 15 min after ALI induction. In vitro AM from mice were cultured for analyses of TNF mRNA expression and protein and adenosine3’:5’-cyclic monophosphate (cAMP) levels. One hour after LPS, the TNF and cAMP levels in AM were measured by ELISA. RT-PCR was used to measure TNF mRNA in AM. The LLLT was inefficient in potentiating the rolipram effect in presence of a TNF synthesis inhibitor. LLLT attenuated the neutrophil influx and TNF in BALF. In AM, the laser increased the cAMP and reduced the TNF-α mRNA. LLLT increases indirectly the cAMP in AM by a TNF-dependent mechanism.
Similar content being viewed by others
References
Beutler B, Milsarek I, Cerami A (1985) Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin. Science 229:869–871
Ulich T, Watson L, Yin S, Guo K, Del Castillo J (1991) The intratracheal administration of endotoxin and cytokines. I: Characterization of LPS-induced TNF-α and IL-1β mRNA expression and the LPS, TNF-α, and IL-1β-induced inflammatory infiltrate. Am J Pathol 138:1485–1496
Ulich T, Yin S, Remick D, Russell D, Eisenberg S, Kohno T (1993) Intratracheal administration of endotoxin and cytokines. IV. The soluble TNF receptor type 1 inhibits acute inflammation. Am J Pathol 142:1335–1338
Denis M, Guojian L, Widmer M, Canin A (1994) A mouse model of lung injury induced by microbial products: implications of tumor necrosis factor. Am J Respir Cell Mol Biol 10:658–664
Moraes V, Vargaftig B, Lefort J, Meager A, Chignard M (1996) Effect of cyclooxygenase inhibitors and modulators of cyclic AMP formation on lipopolysaccharide induced neutrophil infiltration in mouse lung. Br J Pharmacol 117:1792–1796
Kips J, Joos G, Peleman R, Pauwels R (1993) The effect of zardaverine, an inhibitor of phosphodiesterase isoenzymes III and IV, on endotoxin-induced airway changes in rat. Clin Exp Allergy 23:518–523
Tang W, Yi E, Remick D, Wittwer A, Yin S, Qi M, Ulich T (1995) Intratracheal injection of endotoxin and cytokines. IX. Contribution of CD11a/ICAM-1 to neutrophil emigration. Am J Physiol 269:653-669
Howell R, Jenkins L, Howell D (1995) Inhibition of lipopolysaccharide-induced pulmonary edema by isoenzymes-selective phosphodiesterase inhibitors in guinea pigs. J Pharmacol Exp Ther 275:703–709
Spengler R, Spengler M, Lincoln P, Remick D, Strieter R, Kunkel S (1989) Dynamics of dibutyryl cyclic AMP- and prostaglandin E2-mediated suppression of lipopolysaccharide-induced tumor necrosis factor alpha gene expression. Infect Immun 57:2837–2841
Tannenbaun C, Hamilton T (1989) Lipopolysaccharide-induced gene expression in murine peritoneal macrophages is selectively suppressed by agents that elevate intracellular cAMP. J Immunol 142:1274–1280
Prabhakar U, Lipshutz D, Bartus J, Slivjak M, Smith E III, Lee J, Esser K (1994) Characterization of cAMP-dependent inhibition of LPS-induced TNF-α production by rolipram, a specific phosphodiesterase IV (PDE IV) inhibitor. Int J Immunol 16:805–816
Verghese M, McConnell R, Strickland A, Gooding R, Stimpson S, Yarnall D, Taylor D, Furdon P (1995) Differential regulation of human monocyte-derived TNF-α and IL-1β by type IV cAMP-phosphodiesterase (cAMP-PDE) inhibitors. J Pharmacol Exp Ther 272:1313–1320
Zhong W, Burke P, Drotar M, Chavali S, Forse R (1995) Effects of prostaglandin E2, cholera toxin and 8-bromo-cyclic AMP on lipopolysaccharide-induce gene expression of cytokines in human macrophages. Immunol 84:446–452
Turner C, Esser K, Wheeldon E (1993) Therapeutic intervention in a rat model of ARDS: IV. Phosphodiesterase IV inhibition. Cir Shock 39:237–245
Pettipher E, Labasi J, Salter E, Stam E, Cheng J, Griffiths R (1996) Regulation of tumor necrosis factor production by adrenal hormones in vivo: insights into the anti-inflammatory activity of rolipram. Br J Pharmacol 117:1530–1534
Moraes V, Singer M, Vargaftig B, Chignard M (1998) Effects of rolipram on cyclic AMP levels in alveolar macrophages and lipopolysaccharide-induced inflammation in mouse lung. Brit J Pharmacol 123:631–636
Mukhopadhyay S, Hoidal J, Mukherjee T (2006) Role of TNF-alpha in pulmonary pathophysiology. Respir Res 7:1–9
Bjordal J, Bogen B, Lopes-Martins R, Klovning A (2005) Can Cochrane Reviews in controversial areas be biased? A sensitivity analysis based on the protocol of a Systemic Cochrane Review on low-level laser therapy in osteoarthritis. Photomed Laser Surg 23:453–458
Sakurai Y, Yamaguchi M, Abiko Y (2000) Inhibitory effect of low-level laser irradiation on LPS-stimulated prostaglandin E2 production and cycloxygenase-2 in human gingival fibroblasts. Eur J Oral Sci 108:29–34
Campana V, Moya M, Gavotto A, Juri H, Palma J (1999) The relative effects of He-Ne laser and meloxicam on experimentally induced inflammation. Laser Ther 11:36–41
Albertini R, Aimbire F, Correa F, Ribeiro W, Cogo J, Antunes E, Teixeira A, de Nucci G, Castro-Faria-Neto H, Zângaro R, Lopes-Martins R (2004) Effects of different protocol doses of low-power gallium-aluminum-arsenate (Ga-Al-As) laser radiation (650 nm) on carrageenan induced rat paw oedema. J Photochem Photobiol 74:101–107
Rizzi C, Mauriz J, Freitas-Correa D, Moreira A, Zettler C, Filippin L, Marroni N, González-Gallego J (2006) Effects of low-level laser therapy (LLLT) on the nuclear factor (NF)-kappaB signaling pathway in traumatized muscles. Lasers Surg Med 38:704–713
Franco W, Leite R, Parizotto N (2002) Effects of low-intensity infrared laser irradiation on the water transport in the isolated toad urinary bladder. Lasers Surg Med 32:299–304
Kuo Y, Wu W, Wang F (2007) Flashlamp pulsed-dye laser suppressed TGF-beta1 expression and proliferation in cultured keloid fibroblasts in mediated by MAPK pathway. Lasers Surg Med 39:358–364
Albertini R, Aimbire F, Villaverde A, Silva J, Costa M (2007) COX-2 mRNA expression decreases in the subplantar muscle of rat paw subjected to carrageenan-induced inflammation after low-level laser therapy. Inflam Res 56:228–229
Milojevic M, Kuruc V (2003) Laser biostimulation in the treatment of pleurisy. Med Pregl 56:516–520
Landyshev I, Avdeeva N, Goborov N, Krasavina N, Tikhonova G, Tkacheva S (2002) Efficacy of low-intensity irradiation and sodium nedocromil in the complex treatment of patients with bronchial asthma. Ter Arkh 74:25–28
Aimbire F, Albertini R, Pacheco M, Castro-Faria-Neto H, Leonardo P, Iversen V, Lopes-Martins R, Bjordal J (2006) Low-level laser therapy induces dose-dependent reduction of TNF-α level in acute inflammation. Photomed and Laser Surg 24:33–37
Aimbire F, Bjordal J, Iversen V, Albertini R, Frigo L, Pacheco M, Castro-Faria-Neto H, Chavantes M, Labat R, Lopes-Martins R (2006) Low-level laser therapy partially restores trachea muscle relaxation response in rats with tumor necrosis factor-alpha mediated smooth airway muscle dysfunction. Lasers Surg Med 38:773–778
Fels A, Cohn Z (1986) The alveolar macrophage. J Appl Physiol 60:353-369
Thepen T, Van Roojien N, Kraal G (1989) Alveolar macrophage elimination in vivo is associated with an increase in pulmonary immune response in mice. J Exp Med 170:499–509
Sibille Y, Reynolds H (1990) State of the art. Macrophages and polymorphonuclear neutrophils in lung defense and injury. Am Rev J Respir Dis 141:471–481
Meyrick B (1987) Endotoxin-mediated pulmonary endothelial cell injury. Fed Proc 45:19–24
Karu T (1999) Primary and secondary mechanisms of action of visible to near-IR radiation on cells. J Photochem Photobiol 49:1–17
Aimbire F, Albertine R, de Magalhães R, Lopes-Martins R, Castro-Faria-Neto H, Zângaro R, Chavantes M, Pacheco M (2005) Effect of LLLT Ga–Al–As (685 nm) on LPS-induced inflammation of the airway and lung in the rat. Lasers Med Sci 20:11–20
Bjordal J, Johnson M, Iversen V, Aimbire F, Lopes-Martins R (2006) Low-level laser therapy (LLLT) in acute pain. A systematic review of possible mechanism of action and clinical effects in randomized placebo-controlled trials. Photomed Laser Surg 24:158–169
Aimbire F, Lopes-Martins R, Albertini R, Pacheco M, Castro-Faria-Neto H, Leonardo P, Bjordal J (2007) Effect of low-level laser therapy on hemorrhagic lesions induced by immune-complex in rat lungs. Photomed Laser Surg 25:112–117
Aimbire F, Santos F, Albertini R, Castro-Faria-Neto H, Mittmann J, Pacheco-Soares C (2008) Low-level laser therapy decreases levels of lung neutrophils anti-apoptotic factors by a NF-kappaB dependent mechanism. Int Immunopharmacol 8:603–605
Aimbire F, Ligeiro de Oliveira A, Albertini R, Corrêa J, Ladeira de Campos C, Lyon J, Silva J Jr, Costa M (2008) Low- level laser therapy decreases pulmonary microvascular leakage, neutrophil influx and IL-1β levels in airway and lung from rat subjected to LPS-induced inflammation. Inflammation 31:189–197
Mafra de Lima F, Costa M, Albertini R, Silva J Jr, Aimbire F (2009) Low-Level Laser Therapy (LLLT): attenuation of cholinergic hyperreactivity, β2-adrenergic hyporesponsiveness and TNF-alpha mRNA expression in rat bronchi segments in E. coli lipopolysaccharide-induced airway inflammation by a NF-kB-dependent mechanism. Lasers Surg Med 4:68–74
Aimbire F, de Lima F, Costa M, Albertini R, Corrêa J, Iversen V, Bjordal J (2009) Effect of low-level laser therapy on bronchial hyper-responsiveness. Lasers Med Sci 24(4):567–576
Gozzard N, Herd C, Blake S, Holbrook M, Hughes B, Higgs G, Page C (1996) Effects of theophyline and rolipram on antigen-induced airway responses in neonatally immunized rabbits. Br J Pharmacol 117:1405–1412
Acknowledgements
We would like to acknowledge the financial support of Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) – 2008/08048-4 and 2007/02596-7.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
de Lima, F.M., Moreira, L.M., Villaverde, A.B. et al. Low-level laser therapy (LLLT) acts as cAMP-elevating agent in acute respiratory distress syndrome. Lasers Med Sci 26, 389–400 (2011). https://doi.org/10.1007/s10103-010-0874-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10103-010-0874-x