Cooperative induction of histidine decarboxylase (HDC) and histamine H_2 receptor in the infiltrating cells participate in the regulation of inflammation induced by unilateral ureteral obstruction (UUO)

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Objective : Recent accumulating studies have demonstrated that histamine-directed leukocyte migration is mediated by expression of histamine receptor type 2 (H_2R) in target cells and that histamine is involved in innate immune response through H_2R. However, in chronic kidney disease featured by tubulointerstitial fibrosis the underlying molecular mechanism by which histamine acts on leukocyte migration and infiltration into inflamed renal tissue is still unclear. The objective in this study is to elucidate how histamine participate in tubulointerstitial fibrosis. Materials and Methods : To elucidate how histamine participates in the tubulointerstitial fibrosis after unilateral ureteral obstruction (UUO) in C57/BL6 mice we examined both production pathway of histamine and the cells expressing H_2R in the kidney. Results : Continued obstruction progressively induced the expression of H_2R from 2 to 14 days after UUO only in the obstructed kidney. Along with its induction, L-histidine decarboxylase (HDC), which is a key enzyme to produce endogenous histamine from L-histidine, also increased time-dependently in the obstructed kidney. Conversely, the mast cells constitutively expressing HDC were not detectable in the obstructed renal parenchyma except for the restricted region around the renal capsule. Furthermore, the double immunostaining using confocal microscopy demonstrated that the cells expressing H_2R were a subpopulation of the infiltrating cells such as macrophages (F4/80^+) and T-lymphocytes (CD3^+). Conclusions : These findings suggest that histamine is preferentially produced and released from the infiltrating cells associated with induction of HDC in response to inflammatory stimuli and regulates the immune reaction(s) via H_2R-mediated signal transduction pathway in an authocrine and/or paracrine manner in the kidney.
北里大学の論文
2005-03-31

Cooperative induction of histidine decarboxylase (HDC) and histamine H_2 receptor in the infiltrating cells participate in the regulation of inflammation induced by unilateral ureteral obstruction (UUO)

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