Regulation of Cytokine Gene Expression in Mast Cells

Metcalfe, Dean D.

Abstract

It is known that rodent mast cells respond to nerve growth factor (NGF). We have now shown that both the human mast cell line HMC-1 and cultured human mast cells similarly respond to NGF as evidenced by induction of the immediate early gene c-fos through the trkA tyrosine receptor which is phosphorylated on tyrosine residues following NGF exposure. HMC-1 and human mast cells were also found to express NGF mRNA and conditioned media from HMC-1 cells stimulated neurite outgrowth, an effect blocked by anti-NGF. Similarly, we identified the receptor for alpha-melanocyte stimulating hormone (alpha-MSH), MC-1, on murine mast cells. Treatment of mast cells with alpha-MSH increased cAMP levels and down-modulated expression of mRNA for IL-1beta, TNF-alpha, and lymphotactin in activated mast cells. In an animal model of asthma, we have characterized the resident cells responsible for immediate-early IL-4 production following antigen challenge.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Allergy and Infectious Diseases (NIAID)
• Type: Intramural Research (Z01)
• Project #: 1Z01AI000607-08
• Application #: 6098983
• Study Section: Special Emphasis Panel (LAD)
• Support Year: 8
• Fiscal Year: 1998

Institution

• Name: National Institute of Allergy and Infectious Diseases
• Country: United States

Publications

Kulka, M; Metcalfe, D D (2006) TLR3 activation inhibits human mast cell attachment to fibronectin and vitronectin. Mol Immunol 43:1579-86

Metcalfe, Dean D; Boyce, Joshua A (2006) Mast cell biology in evolution. J Allergy Clin Immunol 117:1227-9

Kulka, Marianna; Fukuishi, Nobuyuki; Rottem, Menachem et al. (2006) Mast cells, which interact with Escherichia coli, up-regulate genes associated with innate immunity and become less responsive to Fc(epsilon)RI-mediated activation. J Leukoc Biol 79:339-50

Zudaire, Enrique; Martinez, Alfredo; Garayoa, Mercedes et al. (2006) Adrenomedullin is a cross-talk molecule that regulates tumor and mast cell function during human carcinogenesis. Am J Pathol 168:280-91

Davis, Beverley J; Flanagan, Brian F; Gilfillan, Alasdair M et al. (2004) Nitric oxide inhibits IgE-dependent cytokine production and Fos and Jun activation in mast cells. J Immunol 173:6914-20

Swindle, Emily J; Metcalfe, Dean D; Coleman, John W (2004) Rodent and human mast cells produce functionally significant intracellular reactive oxygen species but not nitric oxide. J Biol Chem 279:48751-9

Woolhiser, Michael R; Brockow, Knut; Metcalfe, Dean D (2004) Activation of human mast cells by aggregated IgG through FcgammaRI: additive effects of C3a. Clin Immunol 110:172-80

Kulka, Marianna; Alexopoulou, Lena; Flavell, Richard A et al. (2004) Activation of mast cells by double-stranded RNA: evidence for activation through Toll-like receptor 3. J Allergy Clin Immunol 114:174-82

Basta, Milan; Van Goor, Fredric; Luccioli, Stefano et al. (2003) F(ab)'2-mediated neutralization of C3a and C5a anaphylatoxins: a novel effector function of immunoglobulins. Nat Med 9:431-8

Okayama, Yoshimichi; Tkaczyk, Christine; Metcalfe, Dean D et al. (2003) Comparison of Fc epsilon RI- and Fc gamma RI-mediated degranulation and TNF-alpha synthesis in human mast cells: selective utilization of phosphatidylinositol-3-kinase for Fc gamma RI-induced degranulation. Eur J Immunol 33:1450-9