PMID- 18524543 OWN - NLM STAT- MEDLINE DCOM- 20081118 LR - 20171116 IS - 0923-1811 (Print) IS - 0923-1811 (Linking) VI - 52 IP - 1 DP - 2008 Oct TI - Regulatory effects of antihistamines on the responses to staphylococcal enterotoxin B of human monocyte-derived dendritic cells and CD4+ T cells. PG - 31-8 LID - 10.1016/j.jdermsci.2008.04.004 [doi] AB - BACKGROUND: Antihistamines are widely used for the treatment of allergic diseases, such as urticaria and allergic rhinitis. They are also effective for the treatment of diseases in which T cells are mainly involved in the pathogenesis, such as atopic dermatitis (AD) and contact dermatitis. Dendritic cells (DCs) drive polarization of naive T cells into Th1 or Th2 subsets, and are also likely to be involved in AD pathogenesis. OBJECTIVES: The aim of this study was to determine the effects of antihistamines on DCs and CD4+ T cells. METHODS: Human monocyte-derived DCs (MoDCs) and autologous CD4+ T cells were obtained from healthy subjects, and cultured together or independently in the presence of antihistamines. As a stimulant, we used staphylococcal enterotoxin B or the combination of anti-CD3 monoclonal antibody (mAb) and anti-CD28 mAb. The concentrations of cytokines and chemokines in culture supernatants were measured by ELISA. The expression of surface molecules on MoDCs was measured by flow cytometry. Cell proliferation in the cocultures of MoDCs and CD4+ T cells (DC-T cocultures) was measured by a [(3)H] thymidine incorporation assay. RESULTS: Antihistamines inhibited the production of IFN-gamma, and enhanced the production of IL-4 in DC-T cocultures. Antihistamines inhibited the production of TNF-alpha, TARC, MDC, IP-10, and Mig from MoDCs. Epinastine, one of antihistamines, suppressed the expression of ICAM-1 (CD54) on MoDCs. Epinastine also inhibited the proliferation of CD4+ T cells cocultured with MoDCs. CONCLUSIONS: Our findings show that antihistamines regulate immune responses by affecting the interaction between DCs and CD4+ T cells, and further DCs and CD4+ T cells independently, which may partially contribute to the control of allergic diseases such as AD and contact dermatitis. FAU - Iida, Hideyuki AU - Iida H AD - Department of Dermatology, Nara Medical University, Kashihara, Japan. hidemaki@naramed-u.ac.jp FAU - Asada, Hideo AU - Asada H FAU - Yokoi, Shoko AU - Yokoi S FAU - Niizeki, Hironori AU - Niizeki H FAU - Yasuda, Yasuki AU - Yasuda Y FAU - Miyagawa, Sachiko AU - Miyagawa S FAU - Kita, Eiji AU - Kita E LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080603 PL - Netherlands TA - J Dermatol Sci JT - Journal of dermatological science JID - 9011485 RN - 0 (Antibodies, Monoclonal) RN - 0 (CCL17 protein, human) RN - 0 (CD28 Antigens) RN - 0 (CD3 Complex) RN - 0 (CXCL10 protein, human) RN - 0 (CXCL9 protein, human) RN - 0 (Chemokine CCL17) RN - 0 (Chemokine CXCL10) RN - 0 (Chemokine CXCL9) RN - 0 (Enterotoxins) RN - 0 (Histamine H1 Antagonists) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Tumor Suppressor Proteins) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) RN - 207137-56-2 (Interleukin-4) RN - 39424-53-8 (enterotoxin B, staphylococcal) RN - 82115-62-6 (Interferon-gamma) RN - EC 3.4.24.- (ADAM Proteins) RN - EC 3.4.24.- (ADAM11 protein, human) SB - IM MH - ADAM Proteins/antagonists & inhibitors/biosynthesis/immunology MH - Adult MH - Antibodies, Monoclonal/immunology MH - CD28 Antigens/immunology/metabolism MH - CD3 Complex/immunology/metabolism MH - CD4-Positive T-Lymphocytes/drug effects/*immunology/metabolism MH - Cell Proliferation/drug effects MH - Chemokine CCL17/biosynthesis MH - Chemokine CXCL10/biosynthesis MH - Chemokine CXCL9/biosynthesis MH - Coculture Techniques MH - Dendritic Cells/drug effects/*immunology/metabolism MH - Enterotoxins/*immunology MH - Histamine H1 Antagonists/*pharmacology MH - Humans MH - Intercellular Adhesion Molecule-1/immunology MH - Interferon-gamma/biosynthesis/*immunology MH - Interleukin-4/biosynthesis/*immunology MH - Middle Aged MH - Tumor Necrosis Factor-alpha/biosynthesis MH - Tumor Suppressor Proteins/antagonists & inhibitors/biosynthesis/immunology EDAT- 2008/06/06 09:00 MHDA- 2008/11/19 09:00 CRDT- 2008/06/06 09:00 PHST- 2007/07/11 00:00 [received] PHST- 2008/03/10 00:00 [revised] PHST- 2008/04/07 00:00 [accepted] PHST- 2008/06/06 09:00 [pubmed] PHST- 2008/11/19 09:00 [medline] PHST- 2008/06/06 09:00 [entrez] AID - S0923-1811(08)00122-9 [pii] AID - 10.1016/j.jdermsci.2008.04.004 [doi] PST - ppublish SO - J Dermatol Sci. 2008 Oct;52(1):31-8. doi: 10.1016/j.jdermsci.2008.04.004. Epub 2008 Jun 3.