Elevated blood and tissue CO(2), or hypercapnia, is common in severe lung disease. Patients with hypercapnia often develop lung infections and have an increased risk of death following pneumonia. To explore whether hypercapnia interferes with host defense, we studied the effects of elevated P(CO2) on macrophage innate immune responses. In differentiated human THP-1 macrophages and human and mouse alveolar macrophages stimulated with lipopolysaccharide (LPS) and other Toll-like receptor ligands, hypercapnia inhibited expression of tumor necrosis factor and interleukin (IL)-6, nuclear factor (NF)-kappaB-dependent cytokines critical for antimicrobial host defense. Inhibition of IL-6 expression by hypercapnia was concentration dependent, rapid, reversible, and independent of extracellular and intracellular acidosis. In contrast, hypercapnia did not down-regulate IL-10 or interferon-beta, which do not require NF-kappaB. Notably, hypercapnia did not affect LPS-induced degradation of IkappaB alpha, nuclear translocation of RelA/p65, or activation of mitogen-activated protein kinases, but it did block IL-6 promoter-driven luciferase activity in mouse RAW 264.7 macrophages. Elevated P(CO2) also decreased phagocytosis of opsonized polystyrene beads and heat-killed bacteria in THP-1 and human alveolar macrophages. By interfering with essential innate immune functions in the macrophage, hypercapnia may cause a previously unrecognized defect in resistance to pulmonary infection in patients with advanced lung disease.
Interleukin-1 (IL-1)-induced inflammatory response in arthritic joints include the enhanced expression and activity of matrix metalloproteinases (MMPs), and their matrix degrading activity contribute to the irreversible loss of cartilage and may also be associated with sustained chronic inflammation. We have earlier shown that green tea (Camellia sinensis) polyphenol epigallocatechin-3-gallate (EGCG) was non-toxic to human chondrocytes [Singh R, Ahmed S, Islam N, Goldberg VM, and Haqqi TM ( Here we show that EGCG at micromolar concentrations was highly effective in inhibiting the IL-1-induced glycosaminoglycan (GAG) release from human cartilage explants in vitro. EGCG also inhibited the IL-1-induced mRNA and protein expression of MMP-1 and MMP-13 in human chondrocytes. Importantly, EGCG showed a differential, dose-dependent inhibitory effect on the expression and activity of MMP-13 and MMP-1. A similar differential dose-dependent inhibition of transcription factors NF-B and AP-1 by EGCG was also noted. These results for the first time demonstrate a differential dosedependent effect of EGCG on the expression and activity of MMPs and on the activities of transcription factors NF-B and AP-1 and provide insights into the molecular basis of the reported anti-inflammatory effects of EGCG. These results also suggest that EGCG or compounds derived from it may be therapeutically effective inhibitors of IL-
This investigation evaluated the relationship between physical fitness and performance of fire suppression tasks. The following mean +/- SD values were associated with 91 fire fighters: age 31.69 +/- 7.39 years, height 177.29 +/- 6.38 cm, weight 83.97 +/- 10.86 kg, % fat 13.78 +/- 4.31, fat free weight (FFW) 71.52 +/- 7.66 kg, pull-ups 9.03 +/- 4.79, push-ups 41.02 +/- 14.08, 1.5 mile run 737.60 +/- 108.11 s, sit and reach 32.00 +/- 8.5 cm, sit-ups 39.88 +/- 7.75, and total grip strength 116.75 +/- 17.67 kg. The physical performance assessment (PPA) consisted of the following: stair climb, hoist, forcible entry, hose advance, and victim rescue. Significant correlations (p < 0.01) were found between the PPA and the following: total grip strength (r = -0.54), FFW (r = -0.47), height (r = -0.40), pull-ups (r = -0.38), push-ups (r = -0.38), 1.5 mile run (r = 0.38), sit-ups (r = -0.32), weight (r = -0.30) and % fat (r = 0.30). Multiple regression analysis indicated that the best multiple predictor of PPA was the 1.5 mile run, FFW, and pull-ups, r = 0.73, p < 0.001. This investigation shows the importance of physical fitness as related to performance of fire suppression job tasks.
Interleukin (IL)-1beta induces the expression of matrix metalloproteinases (MMPs) implicated in cartilage resorption and joint degradation in osteoarthritis (OA). Pomegranate fruit extract (PFE) was recently shown to exert anti-inflammatory effects in different disease models. However, no studies have been undertaken to investigate whether PFE constituents protect articular cartilage. In the present studies, OA chondrocytes or cartilage explants were pretreated with PFE and then stimulated with IL-1beta at different time points in vitro. The amounts of proteoglycan released were measured by a colorimetric assay. The expression of MMPs, phosphorylation of the inhibitor of kappaBalpha (IkappaBalpha) and mitogen-activated protein kinases (MAPKs) was determined by Western immunoblotting. Expression of mRNA was quantified by real-time PCR. MAPK enzyme activity was assayed by in vitro kinase assay. Activation of nuclear factor-kappaB (NF-kappaB) was determined by electrophoretic mobility shift assay. PFE inhibited the IL-1beta-induced proteoglycan breakdown in cartilage explants in vitro. At the cellular level, PFE (6.25-25 mg/L) inhibited the IL-1beta-induced expression of MMP-1, -3, and -13 protein in the medium (P < 0.05) and this was associated with the inhibition of mRNA expression. IL-1beta-induced phosphorylation of p38-MAPK, but not that of c-Jun-N-terminal kinase or extracellular regulated kinase, was most susceptible to inhibition by low doses of PFE, and the addition of PFE blocked the activity of p38-MAPK in a kinase activity assay. PFE also inhibited the IL-1beta-induced phosphorylation of IkappaBalpha and the DNA binding activity of the transcription factor NF-kappaB in OA chondrocytes. Taken together, these novel results indicate that PFE or compounds derived from it may inhibit cartilage degradation in OA and may also be a useful nutritive supplement for maintaining joint integrity and function.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.