The Effects of Interleukin-1βin Tumor Necrosis Factor-α-Induced Acute Pulmonary Inflammation in Mice

Abstract

We determined the role of interleukin-1β (IL-1β) signaling on tumor necrosis factor alpha-induced (TNF-α) lung neutrophil influx as well as neutrophil chemoattractant macrophage inflammatory protein (MIP-2) and KC and soluble TNF-α receptor (TNFR) levels utilizing wildtype (WT), TNF receptor double knockout (TNFR1/TNFR2 KO), and IL-1β KO mice after oropharyngeal instillation with TNF-α. A significant increase in neutrophil accumulation in bronchoalveolar lavage fluid (BALF) and lung interstitium was detected in the WT mice six hours after TNF-α exposure. This correlated with an increase in BALF MIP-2. In contrast, BALF neutrophil numbers were not increased by TNF-α treatment of IL-1β KOs, correlating with a failure to induce BALF MIP-2 and a trend toward increased BALF soluble TNFR1. TNF-α-instillation increased lavage and serum KC and soluble TNFR2 irrespective of IL-1β expression. These results suggest IL-1β contributes, in part, to TNF-α-mediated, chemokine release, and neutrophil recruitment to the lung, potentially associated with altered soluble TNFR1 release into the BALF.

Switch regulation of interleukin-1 beta in downstream of inflammatory cytokines induced by two micro-sized silica particles on differentiated THP-1 macrophages

“…From another viewpoint, the additional inflammation after exposed to IL-1␤ protein might help to explain the progressive inflammation and pulmonary fibrosis even when human are no longer exposed to silica particles, irrespective of ongoing inflammatory responses stimulated by the repeating cycle of alveolar macrophage phagocytosis and cell rupture. It was supported by Saperstein and coworkers findings, which observed that IL-1␤ contributed to chemokine release and neutrophil recruitment in TNF-␣-mediated acute pulmonary inflammation in mice (Saperstein et al, 2009b). However, it is noteworthy that recombinant IL-1␤ protein did not directly induce endogenous IL-1␤ expression on differentiated THP-1 macrophages in this study.…”

Chronic Alcohol Exposure Enhances Lipopolysaccharide-Induced Lung Injury in Mice: Potential Role of Systemic Tumor Necrosis Factor-Alpha

“…Furthermore, increases in these chemokines correlated with increased neutrophil recruitment. Interestingly, increased expression of MIP-2 and KC in the lung and BALF have been shown to be downstream of TNFα signaling (Saperstein et al 2009), which was not enhanced by ethanol pre-exposure in the lung in our model (Figure 4A). In contrast, hepatic TNFα mRNA expression and systemic levels of TNFα were enhanced by the combination of ethanol + LPS (Figure 3A).…”

Azithromycin inhibits macrophage interleukin-1β production through inhibition of activator protein-1 in lipopolysaccharide-induced murine pulmonary neutrophilia

“…Since the promoter region in the IL-1β gene contains binding motifs for AP-1 [35,36] inhibition of its activation will result in reduced IL-1β production. Having in mind that several studies have identified IL-1β as one of the major cytokines driving neutrophil accumulation in lung tissue [26][27][28][29]39,40], inhibition of AP-1 activation and consequent IL-1β production by alveolar macrophages seems to be a sufficient and likely mechanism by which azithromycin reduced neutrophil accumulation in the lungs following LPS challenge (concept summarized in Fig. 9).…”