title: Characterization and function of histamine receptors in human bone marrow stromal cells.
abstract: There are several clinical trials worldwide using bone marrow stromal cells (BMSCs) as a cellular therapy to modulate immune responses in patients suffering from various inflammatory conditions. A deeper understanding of the molecular mechanisms involved in this modulatory effect could help us design better, more effective protocols to treat immune mediated diseases. In this study, we demonstrated that human BMSCs express H1, H2, and H4 histamine receptors and they respond to histamine stimulation with an increased interleukin 6 (IL-6) production both in vitro and in vivo. Using different receptor antagonists, we pinpointed the importance of the H1 histamine receptor, while Western blot analysis and application of various mitogen-activated protein kinase inhibitors highlighted the role of p38, extracellular signal-regulated kinase, and c-Jun N-terminal kinase kinases in the observed effect. When BMSCs were pretreated with either histamine or degranulated human mast cells, they exhibited an enhanced IL-6-dependent antiapoptotic effect on neutrophil granulocytes. Based on these observations, it is likely that introduction of BMSCs into a histamine-rich environment (such as any allergic setting) or pretreatment of these cells with synthetic histamine could have a significant modulatory effect on the therapeutic potential of BMSCs.
authors: National Institutes of Dental and Craniofacial Research, Craniofacial and Skeletal Diseases Branch, NIH, Bethesda, Maryland, USA. nemethk@mail.nih.gov
authors: Krisztian
authors: K
authors: Nemeth
authors: Todd
authors: T
authors: Wilson
authors: Balazs
authors: B
authors: Rada
authors: Alissa
authors: A
authors: Parmelee
authors: Balazs
authors: B
authors: Mayer
authors: Edit
authors: E
authors: Buzas
authors: Andras
authors: A
authors: Falus
authors: Sharon
authors: S
authors: Key
authors: Tamas
authors: T
authors: Masszi
authors: Sarolta
authors: S
authors: Karpati
authors: Eva
authors: E
authors: Mezey
mesh_terms: D000818:Animals; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000378:metabolism* / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D015870:Gene Expression; D006098:Granulocytes / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008297:Male; D008407:Mast Cells / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011968:Receptors, Histamine / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017154:Stromal Cells / Q000378:metabolism* / Q000502:physiology
chemical_list: D015850:Interleukin-6; D016209:Interleukin-8; D011968:Receptors, Histamine; D006632:Histamine