CIRCADIAN MODULATION OF INFLAMMATORY RESPONSE IN MACROPHAGES: ROLE OF TNF RECEPTOR p55 SIGNALING.

ARIAS JOSÉ LUIS; JERÉZ MARÍA BELÉN; DI GENARO MARÍA SILVIA.

Lima

Congreso; Inmunoperu 2012; 2012

ALAI

Biological processes are well organized in time. Relevant immunological parameters display a circadian (approximately 24-h) rhythm. Thus, the pro-inflammatory cytokine production by LPS-stimulated macrophages is determined by the circadian phase of macrophage clock. Moreover, TNF suppresses the expression of clock and clock-controlled genes. Our objective was to study the consequences of TNFRp55 deficiency on the circadian production of pro-inflammatory cytokine by LPS-stimulated macrophages. Thioglycolate-elicited peritoneal macrophages from five C57BL/6 (WT) and TNFRp55-/- mice were harvested, pooled and plated for tissue culture. Individual wells were stimulated for 6 hours with LPS at determined times, and thereafter, supernatants were collected. TNF and IL-6 levels in supernatants were determined by ELISA. We found that TNF and IL-6 response upon LPS stimulation is regulated by intrinsic macrophage clockwork (p<0.01 and p<0.001 for TNF and IL-6, respectively). There was no difference in the amplitude and phase of TNF between WT and TNFRp55-/- macrophages. In contrast, IL-6 levels showed a tendency towards to significant difference in the amplitude between WT versus TNFRp55-/-. These results suggest that TNFRp55 signaling modulates pro-inflammatory cytokine production by macrophage in response to LPS stimulation through a mechanism regulated by a cell-intrinsic local clock.