Histamine Contributes to Tissue Remodeling via Periostin Expression

Histamine is thought to have a critical role in the synthesis of extracellular matrix in skin and may be involved in tissue remodeling of allergic diseases. Recent studies revealed that periostin, a matricelluar protein, contributed to tissue remodeling; however, a link between periostin and histamine remains unproven. We investigated whether periostin was involved in histamine-induced collagen production. Cultured dermal fibroblasts derived from wild-type (WT) or periostin knockout (PN-/-) mice were stimulated with histamine, and then collagen and periostin production was evaluated. Histamine induced collagen gene expression in WT fibroblasts in the late phase but not in the early phase, whereas no effect on collagen expression was observed in histamine-stimulated PN-/- fibroblasts. In WT fibroblasts, histamine directly induced periostin expression in a dose-dependent manner, and an H1 receptor antagonist blocked both periostin and collagen expression. Histamine activated extracellular signal-regulated kinase 1/2 (ERK1/2) through the H1 receptor. Periostin induction was inhibited by either H1 antagonist or ERK1/2 inhibitor treatment in vitro and was attenuated in H1R(-/-) mice. Elevated expression of periostin was found in lesional skin from atopic dermatitis patients. These results suggest that histamine mediates periostin induction and collagen production through activation of the H1 receptor mediated ERK1/2 pathway; furthermore, histamine may accelerate the chronicity of atopic dermatitis.