Please use this identifier to cite or link to this item: http://hdl.handle.net/123456789/898
Title: TLR-mediated albuminuria needs TNFα-mediated cooperativity between TLRs present in hematopoietic tissues and CD80 present on non-hematopoietic tissues in mice
Authors: George, Anna
Jain, Nidhi
Khullar, Bhavya
Oswal, Neelam
Banoth, Balaji
Joshi, Prashant
Ravindran, Balachandran
Panda, Subrat
Basak, Soumen
Rath, Satyajit
Bal, Vineeta
Sopory, Shailaja
Issue Date: Jun-2016
Publisher: The Company of Biologists Ltd.
Abstract: Transient albuminuria induced by pathogen-associated molecular patterns (PAMPs) in mice through engagement of Toll-like receptors (TLRs) is widely studied as a partial model for some forms of human nephrotic syndrome (NS). In addition to TLRs, CD80 has been shown to be essential for PAMP-mediated albuminuria. However, the mechanistic relationships between TLRs, CD80 and albuminuria remain unclear. Here, we show that albuminuria and CD80-uria induced in mice by many TLR ligands are dependent on the expression of TLRs and their downstream signalling intermediate MyD88 exclusively in hematopoietic cells and, conversely, on CD80 expression exclusively in non-hematopoietic cells. TNFα is crucial for TLR-mediated albuminuria and CD80-uria, and induces CD80 expression in cultured renal podocytes. IL-10 from hematopoietic cells ameliorates TNFα production, albuminuria and CD80-uria but does not prevent TNFα-mediated induction of podocyte CD80 expression. Chitohexaose, a small molecule originally of parasite origin, mediates TLR4-dependent anti-inflammatory responses, and blocks TLR-mediated albuminuria and CD80-uria through IL-10. Thus, TNFα is a prominent mediator of renal CD80 induction and resultant albuminuria in this model, and small molecules modulating TLR-mediated inflammatory activation might have contributory or adjunct therapeutic potential in some contexts of NS development.
URI: http://hdl.handle.net/123456789/898
Appears in Collections:Mucosal Immunology, Publications

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