Potential role of store-operated Ca2+ entry in Th2 response induced by histamine in human monocyte-derived dendritic cells

• Published in: International immunopharmacology 2012-02, Vol.12 (2), p.358-367
• Main Authors: Geng, Shuang, Gao, Ya-dong, Yang, Jiong, Zou, Jin-jing, Guo, Wei
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Calcium - metabolism; Calcium Channels - genetics; Calcium Channels - metabolism; Calcium Signaling - drug effects; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - metabolism; Cumulus Cells; Dendritic cells; Dendritic Cells - drug effects; Dendritic Cells - metabolism; Histamine - metabolism; Histamine - pharmacology; Histamine H1 Antagonists - pharmacology; Histamine receptors; Humans; Interleukin-10 - metabolism; Interleukin-12 - metabolism; Medical sciences; Membrane Proteins - genetics; Membrane Proteins - metabolism; Monocytes - drug effects; Monocytes - metabolism; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; ORAI1 Protein; Pharmacology. Drug treatments; Receptors, Histamine - metabolism; Receptors, Histamine H1 - metabolism; Store-operated Ca2 + entry; Stromal Interaction Molecule 1; Th2 Cells - drug effects; Th2 Cells - metabolism
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2011.12.008

Store-operated calcium entry (SOCE) is the main Ca2+ 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 Ca2+ 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 Ca2+ influx through SOCE induced by histamine in Th2 response. We certificate that histamine induced a transient Ca2+ release followed by pronounced Ca2+ influx after re-addition of external Ca2+ which could be inhibited by SOCE blockers SKF-96365 and BTP-2. Moreover, the percentages of DCs that showed an obvious Ca2+ 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 Th2 response of DCs which was through histamine 1 and 4 receptor. ► Store-operated Ca2+ entry (SOCE) participated in the maturation of human dendritic cells (DCs). ► Up-regulation of STIM1 mRNA may contribute to the maturation of DCs induced by histamine. ► We confirmed that histamine promoted the Th2 response via SOCE in DCs. ► Both histamine 1 and 4 receptors took part in the SOCE induced by histamine in DCs.