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Glomerular expression of myxovirus resistance protein 1 in human mesangial cells: Possible activation of innate immunity in the pathogenesis of lupus nephritis
Author(s) -
Watanabe Shojiro,
Imaizumi Tadaatsu,
Tsuruga Kazushi,
Aizawa Tomomi,
Ito Tatsuya,
Matsumiya Tomoh,
Yoshida Hidemi,
Joh Kensuke,
Ito Etsuro,
Tanaka Hiroshi
Publication year - 2013
Publication title -
nephrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 61
eISSN - 1440-1797
pISSN - 1320-5358
DOI - 10.1111/nep.12155
Subject(s) - innate immune system , lupus nephritis , pathogenesis , immunology , interferon , medicine , mesangial cell , nephritis , chemokine , immune system , proinflammatory cytokine , microbiology and biotechnology , biology , inflammation , pathology , kidney , disease
Since viral infections activate type I interferon ( IFN ) pathways and cause subsequent release of IFN ‐dependent proinflammatory chemokines and cytokines, the innate immune system plays an important role in the pathogenesis of lupus nephritis ( LN ). It has been reported that human myxovirus resistance protein 1 ( M x1), a type I IFN ‐dependent transcript, acts against a wide range of RNA viruses. Although the expression of M x1 in biopsy specimens obtained from patients with dermatomyositis and cutaneous lupus has been described, the expression of M x1 in human mesangial cells ( MCs ) has remained largely unknown. We treated normal human MCs in culture with polyinosinic‐polycytidylic acid (poly IC ), an authentic double‐stranded RNA , and analyzed the expression of M x1 by reverse transcription‐polymerase chain reaction and western blotting. To elucidate the poly IC ‐signalling pathway, we subjected the cells to RNA interference against IFN ‐β. We also conducted an immunofluorescence study to examine mesangial M x1 expression in biopsy specimens from patients with LN . Poly IC ‐induced M x1 expression in MCs are shown both time‐ and dose‐dependently, and RNA interference against IFN ‐β inhibited poly IC ‐induced M x1 expression. Intense glomerular M x1 expression was observed in biopsy specimens from patients with LN , whereas negative staining occurred in specimens from patients with IgA nephropathy or purpura nephritis. These preliminary observations support, at least in part, the theory of innate immune system activation in the pathogenesis of LN .