Macrophage migration inhibitory factor regulates interleukin-6 production by facilitating nuclear factor-kappa B activation during Vibrio vulnificus infection
Open Access
- 12 October 2010
- journal article
- Published by Springer Science and Business Media LLC in BMC Immunology
- Vol. 11 (1), 50
- https://doi.org/10.1186/1471-2172-11-50
Abstract
Patients infected with Vibrio vulnificus (V. vulnificus) show severe inflammatory responses characterised by the upregulation of proinflammatory cytokines. Macrophage migration inhibitory factor (MIF), an upstream proinflammatory regulator, increases the inflammation caused by sepsis. Whether MIF regulates responses to V. vulnificus infection and the actual mechanism by which V. vulnificus initiates these MIF-modulated proinflammatory cytokines remain unclear. MIF increased inflammation during V. vulnificus infection in vivo. In V. vulnificus-infected mice, MIF was produced earlier than tumour necrosis factor (TNF)-α and interleukin (IL)-6 and was expressed in a time-dependent manner. ISO-1 ((S, R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester), a small-molecule inhibitor of MIF, significantly decreased IL-6, IL-8, and TNF-α production in a time- and dose-dependent manner in human peripheral blood cells infected with V. vulnificus. The induction of IL-6, IL-8, and TNF-α production by V. vulnificus infection was mediated via the NF-κB- and p38 MAPK-regulated pathways but not via the Akt pathway. ISO-1-treated human peripheral blood cells showed lower V. vulnificus-induced NF-κB activation, IL-6 mRNA expression, and IκB phosphorylation, but they did not show lower p38 MAPK activation. We conclude that MIF regulates V. vulnificus-induced IL-6 production via NF-κB activation and that p38 MAPK activation in V. vulnificus infection is not MIF dependent.Keywords
This publication has 33 references indexed in Scilit:
- Glycogen Synthase Kinase-3β Facilitates IFN-γ-Induced STAT1 Activation by Regulating Src Homology-2 Domain-Containing Phosphatase 2Published by The American Association of Immunologists ,2009
- Role of p38 and Early Growth Response Factor 1 in the Macrophage Response to Group B StreptococcusInfection and Immunity, 2009
- The MIF Receptor CD74 in Diabetic Podocyte InjuryJournal of the American Society of Nephrology, 2009
- Differential and cell‐type specific regulation of responses to Toll‐like receptor agonists by ISO‐1Immunology, 2008
- Vibrio vulnificus Damages Macrophages during the Early Phase of InfectionInfection and Immunity, 2007
- Association between High Levels of Blood Macrophage Migration Inhibitory Factor, Inappropriate Adrenal Response, and Early Death in Patients with Severe SepsisClinical Infectious Diseases, 2007
- INCREASES IN SERUM MACROPHAGE MIGRATION INHIBITORY FACTOR IN PATIENTS WITH SEVERE SEPSIS PREDICT EARLY MORTALITYShock, 2007
- Macrophage migration inhibitory factor (MIF) promotes cell survival by activation of the Akt pathway and role for CSN5/JAB1 in the control of autocrine MIF activityOncogene, 2007
- Macrophage migration inhibitory factor (MIF) regulates host responses to endotoxin through modulation of Toll-like receptor 4 (TLR4)Innate Immunity, 2003
- Macrophage migration inhibitory factor (MIF) regulates host responses to endotoxin through modulation of Toll-like receptor 4 (TLR4)Innate Immunity, 2003