Decrease in IL‐10 and increase in TNF‐α levels in renal tissues during systemic inhibition of nitric oxide in anesthetized mice. Issue 2 (10th February 2014)

• Record Type: Journal Article
• Authors: Singh, Purnima; Castillo, Alexander; Majid, Dewan S. A.
• Is Part Of: Physiological reports. Volume 2:Issue 2(2014:Feb.)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2014-02-10
• Subjects: Physiology -- Periodicals; 571
• DOI: 10.1002/phy2.228
• Languages: English
• ISSNs: 2051-817X

Abstract

<abstract abstract-type="main" id="phy2228-abs-0001"> <title>Abstract</title> <p>Earlier, we demonstrated that the inhibition of nitric oxide synthase (NOS) by nitro‐<sc>l</sc>‐arginine methyl ester (<sc>l</sc>‐NAME) infusion increases the endogenous production of proinflammatory cytokine, tumor necrosis factor (TNF‐<italic>α</italic>). In the present study, we examined the hypothesis that inhibition of nitric oxide (NO) production leads to the suppression of interleukin (IL)‐10 (anti‐inflammatory cytokine) generation which facilitates the enhancement of TNF‐<italic>α</italic> production endogenously. Using appropriate enzyme‐linked immunosorbent assay kits and immunohistochemical staining, the levels of IL‐10 and TNF‐<italic>α</italic> in plasma (P) and in renal tissues (R) were measured in anesthetized mice (C57BL/6; ~10 weeks age; <italic>n</italic> = 6/group) infused with or without <sc>l</sc>‐NAME (200 <italic>μ</italic>g/min/kg; i.v. for 2 h). Compared to vehicle‐treated control mice, <sc>l</sc>‐NAME‐treated mice had a lower level of IL‐10 (P, 0.3 ± 0.1 vs. 2.6 ± 0.6 ng/mL; R, 0.5 ± 0.1 vs. 3 ± 0.1 ng/mg protein) and a higher level of TNF‐<italic>α</italic> (P, 432 ± 82 vs. undetected pg/mL; R, 58 ± 7 vs. 6 ± 5 pg/mg protein). IL‐10 protein expression, present mostly in the distal nephron segments in control mice, was markedly downregulated in <sc>l</sc>‐NAME‐treated mice. Compared to control mice, TNF‐<italic>α</italic> expression increased 2.5‐fold in renal cortical sections (mostly in the distal nephron segments) in <sc>l</sc>‐NAME‐treated mice. Coinfusion of a NO donor, <italic>S</italic>‐nitroso‐<italic>N</italic>‐acetyl‐penicillamine (SNAP; 25 <italic>μ</italic>g/min/kg) with <sc>l</sc>‐NAME in a separate group of mice prevented these changes in IL‐10 and TNF‐<italic>α</italic> induced by <sc>l</sc>‐NAME. IL‐10 infusion (0.075 ng/min/g) in <sc>l</sc>‐NAME‐treated mice markedly attenuated <sc>l</sc>‐NAME‐induced increments in TNF‐<italic>α</italic>. Thus, these results demonstrate that NOS inhibition decreases endogenous IL‐10 generation and thus, minimizes its immune downregulating action on the TNF‐<italic>α</italic> production in the kidney.</p> </abstract>