Histamine induces MUC5AC expression via a hCLCA1 pathway.
BACKGROUND
Histamine is an important inflammatory mediator and associated with early phase allergic response. However, the involvement of histamine in mucin gene expression or production has not been elucidated.


OBJECTIVE
The aim of this study is to investigate whether histamine induces MUC5AC production in NCI-H292 cells, and to evaluate which pathway is involved in this mucin production.


METHODS
MUC5AC production in NCI-H292 cells was analyzed by RT-PCR, immunoassay and immunocytochemical analysis. The effect of histamine on MUC5AC production in these cells at different time courses and concentrations was assessed, and the relationship between hCLCA1 expression and histamine concentration was also evaluated. In addition, cells were pretreated with antihistamine or an hCLCA1 blocker (niflumic acid, NFA) to evaluate the mechanism underlying histamine-induced MUC5AC production.


RESULTS
Histamine upregulated MUC5AC gene expression and mucin protein production in a dose-dependent and time-related fashion. Histamine also dose-dependently increased hCLCA1 mRNA expression. Moreover, pretreatment of cells with chlorpheniramine or NFA reduced histamine-induced MUC5AC mRNA expression and protein production in these cells. The histamine-treated cells showed increased cytoplasmic staining for MUC5AC compared to cells treated with media alone, and cells pretreated with chlorpheniramine or NFA before histamine treatment.


CONCLUSIONS
Our results suggest that histamine-induced MUC5AC production occurs via the upregulation of hCLCA1. It is assumed that antihistamines or hCLCA1 channel blockers can partially suppress histamine-induced MUC5AC production in allergic diseases, e.g. allergic rhinitis.
Kim
Yong Min
YM
Department of Otorhinolaryngology-Head and Neck Surgery, Chungnam National University College of Medicine, Daejeon, Korea.
Won
Tae-Bin
TB
Kim
Si Whan
SW
Min
Yang-Gi
YG
Lee
Chul Hee
CH
Rhee
Chae-Seo
CS
D045744:Cell Line, Tumor; D018118:Chloride Channels / Q000235:genetics / Q000502:physiology*; D002744:Chlorpheniramine / Q000494:pharmacology; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D055271:Mucin 5AC; D009077:Mucins / Q000032:analysis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D011968:Receptors, Histamine / Q000235:genetics
C492109:CLCA1 protein, human; D018118:Chloride Channels; D052246:Cyclooxygenase 2 Inhibitors; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D009077:Mucins; D012333:RNA, Messenger; D011968:Receptors, Histamine; D002744:Chlorpheniramine; D006632:Histamine