IL-2 induces expression and secretion of IFN-gamma in murine peritoneal macrophages.
We investigated the effect of interleukin (IL)-2, a T cell growth factor capable of activating certain macrophage functions, on interferon (IFN)-gamma expression in resting mouse peritoneal macrophages (PM). IL-2 addition to PM from different mouse strains up-modulated IFN-gamma mRNA and protein secretion. It is notable that endogenous type I and II IFNs did not play any role in the IL-2-mediated effect, as comparable levels of secreted IFN-gamma were observed upon IL-2 stimulation of PM from deficient mice. In contrast, endogenous IFN-gamma was requested for the IL-12-induced IFN-gamma production. It is interesting that blocking of each component of the IL-2 receptor (IL-2R) by neutralizing antibodies almost completely abolished IL-2-induced IFN-gamma production, suggesting that all IL-2R chains contribute to the PM biological response to IL-2. The simultaneous treatment of PM with IL-2 and IL-12 resulted in a higher IFN-gamma secretion with respect to that obtained upon treatment with IL-2 or IL-12 alone. It is notable that IFN-gamma protein was expressed intracellularly in the majority of cells exhibiting a macrophage phenotype (i.e., F4/80+) and was secreted upon IL-2 stimulation. Overall, these findings demonstrate that IL-2 regulates at different levels IFN-gamma expression in macrophages, highlighting the crucial role of these cells and their regulated responsiveness to key cytokines in the cross-talk between innate and adaptive immunity.
Puddu
Patrizia
P
Department of Cell Biology and Neurosciences, Viale Regina Elena 299, 00161 Rome, Italy.
Carollo
Maria
M
Pietraforte
Immacolata
I
Spadaro
Francesca
F
Tombesi
Marina
M
Ramoni
Carlo
C
Belardelli
Filippo
F
Gessani
Sandra
S
D000818:Animals; D007371:Interferon-gamma / Q000187:drug effects / Q000235:genetics* / Q000502:physiology*; D018664:Interleukin-12 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008819:Mice, Nude; D010641:Phenotype; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000187:drug effects / Q000276:immunology; D013045:Species Specificity
D007376:Interleukin-2; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D018664:Interleukin-12; D007371:Interferon-gamma