EXPLORING THE IMPACT OF INTERLEUKIN-37 ON PRO-INFLAMMATORY PATHWAYS IN TWO MODELS OF KIDNEY DISEASE
Miss Jemma Gasperoni1, Antony Vinh1, Narbada Saini1, Grant Drummond1, Brooke Huuskes1
1La Trobe University, Bundoora, Australia
Aims: To determine the impact of human interleukin-37 (IL-37) overexpression on renal pro-inflammatory gene expression in two models of kidney disease.
Background: IL-37 is upregulated in response to inflammation and exerts anti-inflammatory properties by preventing IL-18 signalling. Previously, we established causal relationship between IL-18 and the onset of hypertension and kidney impairment, yet the role of IL-37 in regulating IL-18 signalling in kidney disease is unknown.
Methods: Two models of kidney disease were investigated using male C57B6 mice. Firstly, wild-type (WT) and IL-37 overexpressing mice (IL-37Tg) mice underwent uninephrectomy and treated with deoxycorticosterone acetate (2.4 mg/d, s.c.) and saline (0.9%) drinking water (1K/DOCA/salt) and culled after 21 days. Secondly, WT and IL-37Tg mice underwent unilateral ureteral obstruction (UUO) and were culled after 7 days. Kidneys underwent histopathological and gene expression analysis.
Results:
Both models of kidney disease had an altered histoarchitecture, showing tubular atrophy, concurrent with increased collagen deposition (P<0.05 vs WT). The DOCA model demonstrated elevated mRNA expression of Col1a1 and Col3a1 (both P<0.005) compared to WT sham and upregulation in expression of Pro- Il-18 (P<0.01), Ccl2 (P<0.0001), Il-18bp, Il-6, Vcam, Ccl5 and Icam (n=5-13, all P<0.05) compared to WT sham. Similarly, WT UUO mice exhibited an upregulation in expression of Il-18bp, Il-18r1, Il-18rap, Il-1β (n=8; all P<0.001). IL-37Tg mice exhibited a significant increase in IL-37 mRNA (P<0.0001) yet had no effect on fibrosis or pro-inflammatory genes in both models. Interestingly, Pro-IL-18 expression was blunted in IL-37Tg mice (n=13; P=0.0268) compared to WT 1K/DOCA mice, yet downstream cytokines Icam, Vcam, Il-6, and Ccl2, remained unchanged.
Conclusion: IL-37 does not seem be protective against increases in IL-18 signalling in two models of kidney disease.
Presentation Slides PDF – Click here
Biography:
Jemma is a dedicated Research Officer working under the esteemed supervision of Dr. Brooke Huuskes. With a strong focus on understanding the underlying causes of chronic kidney disease, Jemma’s work is at the forefront of nephrology research. Her current project investigates the role of Interleukin-37 overexpression in modulating inflammatory responses in kidney disease models. This innovative research aims to shed light on the complex mechanisms of kidney disease and potentially pave the way for novel therapeutic strategies.