Atopic Dermatitis-Like Chronic Inflammation May Be Associated with Kidney Inflammation

Background: Cross-sectional and case control studies recently indicated the association between renal abnormalities and atopic dermatitis (AD). AD causes not only skin lesions, but also the dysregulation of a wide range of cytokines in the serum. S100A8/9 is one of the calcium binding proteins belonging to the S100 family, derived from neutrophils and macrophages, and also involved in chronic inflammatory diseases such as AD. However, the underlying mechanism of S100A8/9 for a potential link between kidney diseases and AD remains unknown. Methods: To evaluate the status of kidney functions of patients with AD, we analyzed the serum and urine samples of US adults from the National Health and Nutrition Examination Survey (NHANES). In addition, a chronic AD-like mouse model was induced by repeatedly applying 2,4-dinitrochlorobenzene on the ears and back. The renal function was evaluated by urine and serum examinations, histological staining and electron microscopy imaging of kidneys. The expression of glomerular filtration barrier proteins was evaluated by immunoblotting and immunofluorescence staining. Furthermore, real-time PCR and ELISA assays were performed both in vivo and in vitro to analyze kidney inflammation. Results: Analysis of NHANES data confirmed the upregulation of urine protein creatinine ratio and downregulation of estimate GFR in patients with AD compared to the healthy subjects. In addition, AD-like mice showed higher albuminuria and serum creatinine than control mice. Moreover, these mice had an increase in glomerular cell infiltration, including neutrophils and macrophages, and foot process effacement of podocytes, indicating dysfunction of glomerular filtration by AD-like inflammation. Kidneys from AD mice showed downregulated expression of glomerular filtration barrier proteins. Concurrently, S100A8/9 was found to be elevated in the serum and renal cortex of these mice. Expression of S100A8/9 in the renal cortex correlated with the status of albuminuria and AD-like inflammation. Conclusion: Our findings suggest that dysfunctional glomerular filtration and reduced kidney function in AD-like mice might be correlated with the increased levels of S100A8/9 derived from neutrophils and macrophages.