IL-10 Deficiency Aggravates Renal Inflammation, Fibrosis and Functional Failure in High-Fat Dieted Obese Mice.

Affiliation

Kim DH(#)(1), Chun SY(#)(2), Lee E(3), Kim B(2), Yoon B(2), Gil H(2), Han MH(3), Ha YS(4), Lee JN(5), Kwon TG(5), Kim BS(#)(6), Jang BI(#)(7).
Author information:
(1)Department of Laboratory Animal Research Support Team, Yeungnam University Medical Center, Daegu, 42415, Republic of Korea.
(2)BioMedical Research Institute, Kyungpook National University Hospital, Daegu, 41944, Republic of Korea.
(3)Department of Pathology, School of Medicine, Kyungpook National University, Daegu, 41944, Republic of Korea.
(4)Department of Urology, Kyungpook National University Chilgok Hospital, Daegu, Korea.
(5)Department of Urology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
(6)Department of Urology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea. [Email]
(7)Department of Internal Medicine, School of Medicine, Yeungnam University, Daegu, Republic of Korea. [Email]
(#)Contributed equally

Abstract

BACKGROUND: High-fat diet-induced obesity is one of the major cause of chronic renal failure. This obesity-related renal failure is mainly caused by inflammatory processes. However, the role of the major anti-inflammatory cytokine interleukin (IL)-10 has not been researched intensively. METHODS: To evaluate the effect of IL-10 deficiency on obesity-related renal failure, the in vivo study was carried with four animal groups; (1) Low-fat dieted C57BL/6 mice, (2) Low-fat dieted IL-10 knockout (KO) mice, (3) High-fat dieted C57BL/6 mice and (4) High-fat dieted IL-10 KO mice group. The analysis was carried with blood/urine chemistry, H&E, Oil-Red-O, periodic acid-Schiff and Masson's trichrome staining immunohistochemistry and real-time PCR methods. RESULTS: At week 12, high-fat dieted IL-10 KO mice showed 1) severe lipid accumulation in kidneys, cholesterol elevation (in total, serum kidney) and low-density lipoprotein increasion through the SCAP-SREBP2-LDLr pathway; (2) serious histopathologic alterations showing glomerulosclerosis, tubulointerstitial fibrosis and immune cell infiltration; (3) increased pro-inflammatory cytokines and chemokines expression; (4) enhanced renal fibrosis; and (5) serious functional failure with high serum creatinine and BUN and proteinuria excretion compared to other groups. CONCLUSION: IL-10 deficiency aggravates renal inflammation, fibrosis and functional failure in high-fat dieted obese mice, thus IL-10 therapy could be applied to obesity-related chronic renal failure.