prodigiosin and Arthritis--Rheumatoid

Prodigiosin (PRO) is a natural pigment that possesses multiple activities, covering anti-tumor, anti-bacteria, and immunosuppression. This study is committed to an investigation into the underlying function and the certain mechanism of PRO in acute lung damage followed by rheumatoid arthritis (RA). Cecal ligation and puncture (CLP) method was implemented to trigger a rat lung injury model, and a rat RA model was constructed with the help of rheumatoid arthritis induced by collagen. Prodigiosin was administered to intervene in the rats' lung tissues post-treatment. The expressions of pro-inflammatory cytokines (interleukin-1beta, interleukin-6, tumor necrosis factor-alpha, and monocyte chemoattractant protein-1 were determined. Western blot was carried out to detect anti-surfactant protein A (SPA), anti-surfactant protein D (SPD), apoptosis-concerned proteins (Bax, cleaved-caspase-3, Bcl-2, and pro-caspase-3), the nuclear factor-kappaB (NF-κB)/nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3)/apoptosis-concerned speckle-like protein (ASC)/caspase-1 signaling pathway. The apoptosis of pulmonary epithelial tissues was checked via TUNEL assay, as corresponding kits were adopted to confirm the activity of lactate dehydrogenase (LDH) and the levels of oxidative stress markers malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px). Prodigiosin ameliorated the pathological damage of CLP rats. Prodigiosin alleviated the production of inflammatory and oxidative stress mediators. In the RA rats with acute lung injury, prodigiosin hampered apoptosis in the lung. Mechanistically, prodigiosin hinders the activation of the NF-κB/NLRP3 signaling axis. In conclusion: prodigiosin relieves acute lung injury in a rat model of rheumatoid arthritis by exerting anti-inflammatory and anti-oxidative effects through downregulating the NF-κB/NLRP3 signaling axis.

Topics: Acute Lung Injury; Animals; Arthritis, Rheumatoid; Leucine; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Nucleotides; Prodigiosin; Pyrin Domain; Rats; Signal Transduction

Prodigiosin (PDG) is a microbial red dye with antioxidant and anti-inflammatory properties, although its effect on rheumatoid arthritis (RA) remains uncertain. Also, multiple doses of low dose γ- radiation (LDR) have been observed to be as a successful intervention for RA. Thus, the purpose of this study was to investigate the ameliorative potential of PDG and/or LDR on adjuvant-induced arthritis (AIA) in rats.. The anti-inflammatory and anti-arthritic effects of PDG and/or LDR were examined in vitro and in vivo, respectively. In the AIA model, the arthritic indexes, paw swelling degrees, body weight gain, and histopathological assessment in AIA rats were assayed. The impact of PDG (200 µg/kg; p.o) and/or LDR (0.5 Gy) on the levels of pro- and anti-inflammatory cytokines (IL-1β, TNF-α, IL-6, IL-18, IL-17A, and IL-10) as well as the regulation of osteoprotegrin (OPG)/ receptor activator of nuclear factor κB ligand (RANKL)/ nuclear factor-κB (NF-κB)/MMP-13 pathways was determined. Methotrexate (MTX; 0.05 mg/kg; twice/week, i.p) was administered concurrently as a standard anti-arthritic drug.. PDG and/or LDR markedly diminished the arthritic indexes, paw edema, weigh loss in AIA rats, alleviated the pathological alterations in joints, reduced the levels of pro-inflammatory cytokines IL-1β, TNF-α, IL-6, IL-18, IL-17A, and RANKL in serum and synovial tissues, while increasing anti-inflammatory cytokines IL-10 and OPG levels. Moreover, PDG and/or LDR down-regulated the expression of RANKL, NF-κBp65, MMP13, caspase-3, and decreased the RANKL/OPG ratio, whereas OPG and collagen II were enhanced in synovial tissues.. PDG and/or LDR exhibited obvious anti-RA activity on AIA.

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Arthritis, Rheumatoid; Cytokines; Interleukin-10; Interleukin-17; Interleukin-18; Interleukin-6; Matrix Metalloproteinase 13; Methotrexate; NF-kappa B; Prodigiosin; Rats; Tumor Necrosis Factor-alpha

Topics: Adult; Arthritis, Rheumatoid; Chloroquine; Female; Humans; Male; Middle Aged; Periodontal Diseases; Prodigiosin; Pyrogens