Potential role of store-operated Ca2+ entry in Th2 response induced by histamine in human monocyte-derived dendritic cells.
Store-operated calcium entry (SOCE) is the main Ca(2+) influx pathway of dendritic cells (DCs). DCs primed with histamine facilitate Th2 immune response via different types of histamine receptors. Histamine induces DCs to release Ca(2+) from internal store. Therefore, we wonder that whether histamine could activate SOCE in DCs through its receptors, and what's the functional relevance of the Ca(2+) influx through SOCE induced by histamine in Th(2) response. We certificate that histamine induced a transient Ca(2+) release followed by pronounced Ca(2+) influx after re-addition of external Ca(2+) which could be inhibited by SOCE blockers SKF-96365 and BTP-2. Moreover, the percentages of DCs that showed an obvious Ca(2+) release response to histamine were decreased in the presence of histamine 1 (H1) receptor antagonist pyridylethylamine (Pyr) or histamine 4 (H4) receptor antagonist JNJ7777120 (JNJ). Histamine up-regulated the mRNA expression of STIM1 in DCs, one of the two major proteins of SOCE channel. SOCE blocker BTP-2 and histamine receptor antagonists JNJ and Pyr inhibited the increase of CD86 induced by histamine on DCs. Histamine increased the level of IL-10 and decreased the level of IL-12p70 secreted by DCs. SOC blockers SKF and BTP-2 inhibited the level of both IL-10 and IL-12p70 secreted by DCs. Pretreatment of SOC blockers and H1, H4 receptor antagonists with DCs inhibited the Th2 polarization of T helper cells induced by histamine in mixed lymphocyte responses (MLR). We demonstrated that SOCE was involved in histamine-induced maturation and Th(2) response of DCs which was through histamine 1 and 4 receptor.
Department of Respiratory Medicine, Zhongnan Hospital, Wuhan, Donghu Road 169, 430071 Wuhan, China.
Shuang
S
Geng
Ya-dong
YD
Gao
Jiong
J
Yang
Jin-jing
JJ
Zou
Wei
W
Guo
D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D054885:Cumulus Cells; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism*; D006632:Histamine / Q000378:metabolism / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D000071740:ORAI1 Protein; D011968:Receptors, Histamine / Q000378:metabolism; D011969:Receptors, Histamine H1 / Q000378:metabolism; D000071737:Stromal Interaction Molecule 1; D018418:Th2 Cells / Q000187:drug effects / Q000378:metabolism*
D015220:Calcium Channels; D006634:Histamine H1 Antagonists; C508609:IL10 protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; D011968:Receptors, Histamine; D011969:Receptors, Histamine H1; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1; D016753:Interleukin-10; D018664:Interleukin-12; D006632:Histamine; D002118:Calcium