Interferon-gamma Regulates Chemokine Expression and Release in the Human Mast Cell Line HMC1: Role of Nitric Oxide

Overview

Journal Immunology

Specialty Allergy & Immunology

Date 2007 Jul 31

PMID 17662042

Citations 3

Authors

M Gilchrist

A D Befus

Affiliations

Soon will be listed here.

Abstract

Mast cells (MCs) are critical immune effector cells that release cytokines and chemokines involved in both homeostasis and disease. Interferon-gamma (IFN-gamma) is a pleiotropic cytokine that regulates multiple cellular activities. IFN-gamma modulates rodent MC responsiveness via production of nitric oxide (NO), although the effects in human MC populations is unknown. We sought to investigate the effects of IFN-gamma on expression of the chemokines interleukin-8 (IL-8) and CCL1 (I-309) in a human mast cell line (HMC1) and to determine the underlying regulatory mechanism. Nitric oxide synthase (NOS), IL-8 and CCL1 expression was determined using real-time polymerase chain reaction (PCR). NOS protein expression was analysed using western blot. NOS activity was determined using the citrulline assay. IL-8 and CCL1 release was measured by specific enzyme-linked immunosorbent assay (ELISA). IFN-gamma inhibited phorbol 12-myristate 13-acetate (PMA)-induced release of IL-8 and CCL1 (by 47 and 38%). Real-time PCR analysis of IFN-gamma-treated HMC1 showed a significant (P < 0.05) time-dependent increase in NOS1 and NOS3 mRNA. NOS3 protein was significantly increased at 18 hr, which correlated with a significant (P < 0.05) increase in constitutive NOS (cNOS) activity. IFN-gamma-induced inhibition of chemokine expression and release was NO dependent, as treatment with the NOS inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME) reduced the IFN-gamma inhibitory effect on IL-8 and CCL1 mRNA expression. NO donors mimicked the IFN-gamma effect. IFN-gamma inhibited PMA-induced cAMP response element binding protein (CREB) phosphorylation and DNA-binding activity. Our observations indicate for the first time that IFN-gamma enhances endogenous NO formation through NOS3 activity, and that NO regulates the transcription and release of IL-8 and CCL1 in a human MC line.

Citing Articles

Pyromeconic acid-enriched Erigeron annuus water extract as a cosmetic ingredient for itch relief and anti-inflammatory activity.

Kang M, Kang M, Kim T, Jeong S, Oh S Sci Rep. 2024; 14(1):4698.

PMID: 38409467 PMC: 10897215. DOI: 10.1038/s41598-024-55365-2.

Zika Virus Infects Human Placental Mast Cells and the HMC-1 Cell Line, and Triggers Degranulation, Cytokine Release and Ultrastructural Changes.

Rabelo K, Goncalves A, de Souza L, Sales A, de Lima S, Trindade G Cells. 2020; 9(4).

PMID: 32316163 PMC: 7227014. DOI: 10.3390/cells9040975.

Effect of rifampin on production of inflammatory mediators in HepG2 liver epithelial cells.

Yuhas Y, Berent E, Ashkenazi S Antimicrob Agents Chemother. 2011; 55(12):5541-6.

PMID: 21930886 PMC: 3232822. DOI: 10.1128/AAC.05149-11.

References

Thomassen M, Raychaudhuri B, Dweik R, Farver C, Buhrow L, Malur A . Nitric oxide regulation of asthmatic airway inflammation with segmental allergen challenge. J Allergy Clin Immunol. 1999; 104(6):1174-82. DOI: 10.1016/s0091-6749(99)70010-2. View

Eastmond N, Banks E, Coleman J . Nitric oxide inhibits IgE-mediated degranulation of mast cells and is the principal intermediate in IFN-gamma-induced suppression of exocytosis. J Immunol. 1997; 159(3):1444-50. View

Okayama Y, Kirshenbaum A, Metcalfe D . Expression of a functional high-affinity IgG receptor, Fc gamma RI, on human mast cells: Up-regulation by IFN-gamma. J Immunol. 2001; 164(8):4332-9. DOI: 10.4049/jimmunol.164.8.4332. View

Wedemeyer J, Tsai M, Galli S . Roles of mast cells and basophils in innate and acquired immunity. Curr Opin Immunol. 2000; 12(6):624-31. DOI: 10.1016/s0952-7915(00)00154-0. View

Shtrichman R, Samuel C . The role of gamma interferon in antimicrobial immunity. Curr Opin Microbiol. 2001; 4(3):251-9. DOI: 10.1016/s1369-5274(00)00199-5. View

Panina-Bordignon P, Papi A, Mariani M, Di Lucia P, Casoni G, Bellettato C . The C-C chemokine receptors CCR4 and CCR8 identify airway T cells of allergen-challenged atopic asthmatics. J Clin Invest. 2001; 107(11):1357-64. PMC: 209325. DOI: 10.1172/JCI12655. View

Natarajan R, Gupta S, Fisher B, Ghosh S, Fowler 3rd A . Nitric oxide suppresses IL-8 transcription by inhibiting c-Jun N-terminal kinase-induced AP-1 activation. Exp Cell Res. 2001; 266(2):203-12. DOI: 10.1006/excr.2001.5218. View

Gurish M, Austen K . The diverse roles of mast cells. J Exp Med. 2001; 194(1):F1-5. PMC: 2193445. DOI: 10.1084/jem.194.1.f1. View

Alderton W, Cooper C, Knowles R . Nitric oxide synthases: structure, function and inhibition. Biochem J. 2001; 357(Pt 3):593-615. PMC: 1221991. DOI: 10.1042/0264-6021:3570593. View

10.

Salvi S, Babu K, Holgate S . Is asthma really due to a polarized T cell response toward a helper T cell type 2 phenotype?. Am J Respir Crit Care Med. 2001; 164(8 Pt 1):1343-6. DOI: 10.1164/ajrccm.164.8.2103080. View

11.

Muhl H, Dinarello C . Macrophage inflammatory protein-1 alpha production in lipopolysaccharide-stimulated human adherent blood mononuclear cells is inhibited by the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine. J Immunol. 1997; 159(10):5063-9. View

12.

Bacci S, Rucci L . Colocalization of tumor necrosis factor-alpha and nitric oxide-synthase immunoreactivity in mast cell granules of nasal mucosa. Histol Histopathol. 1998; 13(4):1011-4. DOI: 10.14670/HH-13.1011. View

13.

De Sanctis G, MacLean J, Hamada K, Mehta S, Scott J, Jiao A . Contribution of nitric oxide synthases 1, 2, and 3 to airway hyperresponsiveness and inflammation in a murine model of asthma. J Exp Med. 1999; 189(10):1621-30. PMC: 2193630. DOI: 10.1084/jem.189.10.1621. View

14.

Swindle E, Metcalfe D, Coleman J . Rodent and human mast cells produce functionally significant intracellular reactive oxygen species but not nitric oxide. J Biol Chem. 2004; 279(47):48751-9. DOI: 10.1074/jbc.M409738200. View

15.

Davis B, Flanagan B, Gilfillan A, Metcalfe D, Coleman J . Nitric oxide inhibits IgE-dependent cytokine production and Fos and Jun activation in mast cells. J Immunol. 2004; 173(11):6914-20. DOI: 10.4049/jimmunol.173.11.6914. View

16.

Wu J, Bennett A . Essential role for mitogen-activated protein (MAP) kinase phosphatase-1 in stress-responsive MAP kinase and cell survival signaling. J Biol Chem. 2005; 280(16):16461-6. DOI: 10.1074/jbc.M501762200. View

17.

Fish J, Matouk C, Rachlis A, Lin S, Tai S, DAbreo C . The expression of endothelial nitric-oxide synthase is controlled by a cell-specific histone code. J Biol Chem. 2005; 280(26):24824-38. DOI: 10.1074/jbc.M502115200. View

18.

Mann-Chandler M, Kashyap M, Wright H, Norozian F, Barnstein B, Gingras S . IFN-gamma induces apoptosis in developing mast cells. J Immunol. 2005; 175(5):3000-5. DOI: 10.4049/jimmunol.175.5.3000. View

19.

Riccio A, Alvania R, Lonze B, Ramanan N, Kim T, Huang Y . A nitric oxide signaling pathway controls CREB-mediated gene expression in neurons. Mol Cell. 2006; 21(2):283-94. DOI: 10.1016/j.molcel.2005.12.006. View

20.

Gobeil Jr F, Zhu T, Brault S, Geha A, Vazquez-Tello A, Fortier A . Nitric oxide signaling via nuclearized endothelial nitric-oxide synthase modulates expression of the immediate early genes iNOS and mPGES-1. J Biol Chem. 2006; 281(23):16058-67. DOI: 10.1074/jbc.M602219200. View