title: Histamine inhibits the production of interferon-induced protein of 10 kDa in human squamous cell carcinoma and melanoma.
abstract: Interferon-induced protein of (IP-10) inhibits tumor progression. Tumor cells can produce interferon-induced protein of IP-10 in response to interferon-g. Histamine in the vicinity of tumor cells may sustain the tumor progression. We examined the in vitro effects of histamine on interferon-induced protein of IP-10 production in human squamous cell carcinoma and melanoma. Histamine suppressed interferon-g-mediated interferon-induced protein of IP-10 secretion and mRNA expression in SV40-transformed keratinocytes, SCC15, SCC4, and melanoma WM115, WM266-4, and C32. Histamine suppressed interferon-g-induced interferon-mediated protein of IP-10 promoter activation in these cells, and the interferon-stimulated response element on the promoter was responsible for the suppression. Histamine suppressed interferon-g-mediated transcription through the interferon-stimulated response element and signal transducer and activator of transcription 1alpha binding to the interferon-stimulated response element. Histamine suppressed interferon-g-induced tyrosine phosphorylation of the signal transducer and activator of transcription 1alpha, Janus tyrosine kinase 1, and Janus tyrosine kinase 2. Histamine-mediated suppression on the interferon-g-induced interferon-mediated protein of IP-10 synthesis was counteracted by the H2 receptor antagonist cimetidine, adenylate cyclase inhibitor SQ22536, and protein kinase A inhibitor H-89, but were not affected by H1 receptor antagonist mepyramine. Cimetidine, SQ22536, and H-89 also counteracted histamine-mediated suppression on the interferon-g-induced transcription through the interferon-stimulated response element, signal transducer and activator of transcription 1alpha binding to the interferon-stimulated response element, and tyrosine phosphorylation of the signal transducer and activator of transcription 1alpha, Janus tyrosine kinase 1, and Janus tyrosine kinase 2. Histamine increased intracellular 3',5'-adenosine cyclic monophosphate level and protein kinase A activity in squamous cell carcinoma and melanoma, and the effects of histamine were blocked by cimetidine. These results suggest that histamine may interact with H2 receptor on squamous cell carcinoma and melanoma and generate 3',5'-adenosine cyclic monophosphate, which may activate protein kinase A. The cyclic 3',5'-adenosine monophosphate/protein kinase A signaling pathway induced by histamine may inhibit interferon-g-induced signal transducer and activator of transcription 1alpha activation and suppress interferon-induced protein of IP-10 synthesis.
authors.affiliation: Department of Dermatology, Teikyo University, School of Medicine, 11-1, Kaga-2, Itabashi-Ku, Tokyo 173-8605, Japan. nmk@med.teikyo-u.ac.jp
authors.forename: Naoko
authors.initials: N
authors.lastname: Kanda
authors.forename: Shinichi
authors.initials: S
authors.lastname: Watanabe
mesh_terms: D002294:Carcinoma, Squamous Cell; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000235:genetics* / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006632:Histamine / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D050832:Interferon-Stimulated Gene Factor 3; D007371:Interferon-gamma / Q000494:pharmacology; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D008545:Melanoma; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000032:analysis; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine / Q000235:genetics; D011969:Receptors, Histamine H1 / Q000235:genetics; D011970:Receptors, Histamine H2 / Q000235:genetics; D018100:Receptors, Histamine H3 / Q000235:genetics; D000074040:Receptors, Histamine H4; D020218:Response Elements / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D012878:Skin Neoplasms; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism
chemical_list: D054357:Chemokine CXCL10; D019743:Chemokines, CXC; C418607:HRH4 protein, human; D050832:Interferon-Stimulated Gene Factor 3; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D018100:Receptors, Histamine H3; D000074040:Receptors, Histamine H4; D014157:Transcription Factors; C079868:gamma interferon activation factor; D014443:Tyrosine; D006632:Histamine; D007371:Interferon-gamma; D000242:Cyclic AMP; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; C507924:JAK2 protein, human; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases