Type I Interferon regulates cytokine-delayed neutrophil apoptosis, reactive oxygen species production and chemokine expression.

Type I Interferon regulates cytokine-delayed neutrophil apoptosis, reactive oxygen species production and chemokine expression. Clin Exp Immunol. 2020 Sep 29;: Authors: Glennon-Alty L, Moots RJ, Edwards SW, Wright HL Abstract Interferons (IFNs) are key regulators of a number of inflammatory conditions in which neutrophils play an important role in pathology, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), where Type I IFNs are implicated in disease pathology. However, IFNs are usually generated in vivo together with other cytokines that also have immunoregulatory functions but such interactions are poorly-defined experimentally. We measured the effects of Type-I (IFNα) IFN, elevated in both RA and SLE, on the functions of healthy neutrophils incubated in vitro in the absence and presence of pro-inflammatory cytokines typically elevated in inflammatory diseases (TNFα, GM-CSF). IFNα alone had no effect on neutrophil apoptosis, however it did abrogate the anti-apoptotic effect of GM-CSF (18h, p<0.01). The enhanced stabilty of the anti-apoptotic protein Mcl-1 and delayed activation of caspase activation normally regulated by GM-CSF were blocked by IFNα: this effect was mediated, in part, by activation of p38 MAPK. IFNα alone also primed ROS production and maintained the transient priming effect of TNFα for up to 4h: it also down-regulated GM-CSF- and TNFα-activated expression of CXCL1, CXCL2, CXCL3, CX...
Source: Clinical and Developmental Immunology - Category: Allergy & Immunology Authors: Tags: Clin Exp Immunol Source Type: research