Modulation of lung allergic response by renal ischemia and reperfusion injury

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundacao de Auxilio aos Docentes e Alunos-UNIFESP (FADA) Complex Fluids INCT Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) The Th1/Th2 balance represents an important factor in the pathogenesis of renal ischemia-reperfusion injury (IRI). in addition, IRI causes a systemic inflammation that can affect other tissues, such as the lungs. To investigate the ability of renal IRI to modulate pulmonary function in a specific model of allergic inflammation, C57Bl/6 mice were immunized with ovalbumin/albumen on days 0 and 7 and challenged with an ovalbumin (OA) aerosol on days 14 and 21. After 24 h of the second antigen challenge, the animals were subjected to 45 minutes of ischemia. After 24 h of reperfusion, the bronchoalveolar lavage (BAL) fluid, blood and lung tissue were collected for analysis. Serum creatinine levels increased in both allergic and non-immunized animals subjected to IRI. However, BAL analysis showed a reduction in the total cells (46%) and neutrophils (58%) compared with control allergic animals not submitted to IRI. in addition, OA challenge induced the phosphorylation of ERK and Akt and the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lung homogenates. After renal IRI, the phosphorylation of ERK and expression of COX-2 and iNOS were markedly reduced; however, there was no difference in the phosphorylation of Akt between sham and ischemic OA-challenged animals. Mucus production was also reduced in allergic mice after renal IRI. IL-4, IL-5 and IL-13 were markedly down-regulated in immunized/challenged mice subjected to IRI. These results suggest that renal IRI can modulate lung allergic inflammation, probably by altering the Th1/Th2 balance and, at least in part, by changing cellular signal transduction factors. Copyright (C) 2012 S. Karger AG, Basel Universidade Federal de São Paulo, Dept Ciencias Biol, Diadema, SP, Brazil Univ São Paulo, Fac Ciencias Farmaceut, Dept Anal Clin & Toxicol, São Paulo, Brazil Universidade Federal de São Paulo, Disciplina Nefrol, Lab Imunol Clin & Expt, São Paulo, Brazil Univ São Paulo, Inst Ciencias Biomed, Dept Imunol, BR-05508 São Paulo, Brazil Universidade Federal de São Paulo, Dept Ciencias Biol, Diadema, SP, Brazil Universidade Federal de São Paulo, Disciplina Nefrol, Lab Imunol Clin & Expt, São Paulo, Brazil FAPESP: 07/07139-3 FAPESP: 10/01404-0 Web of Science