Immunomodulatory effect of curcumin on lipopolysaccharide‐ and/or flagellin‐induced production of prostaglandin E2 and relative expression of proinflammatory cytokines in the primary bubaline endometrial stromal cells

Abstract

Contents Developing alternate therapies for bovine endometritis is important in the context of drug residues in the milk and emergence of antimicrobial resistant bacteria. In this regard, we studied the immunomodulatory effect of curcumin 30 µM, on lipopolysaccharide‐ (LPS) and/or flagellin (100 ng/ml each)‐induced prostaglandin E2 (PGE2) and proinflammatory cytokines (PIC) using primary bubaline endometrial stromal cells. After 24 hr treatment, the supernatant was assayed for PGE2 while cells were used for relative quantification of cytokines like IL‐1β, IL‐6, IL‐8 and TNF α transcripts using a control group as calibrator. LPS was found to possess potent stimulatory effect on PGE2 production, whereas the flagellin was not as potent as LPS in stimulating the PGE2 production either per se or in combination with LPS. LPS markedly up‐regulated the transcripts of IL‐8 and IL‐6 as compared to IL‐1β and TNF α in the bubaline endometrial stromal cells. Except for IL‐8, flagellin did not up‐regulate other PICs. There was no additive effect between LPS and flagellin on the up‐regulation of inflammatory cytokines. Curcumin inhibited the LPS‐induced up‐regulation of PIC with strong down‐regulation of IL‐8. The inhibitory effects of curcumin on the inflammatory mediators suggest a potential in the treatment of bovine endometritis.

Bovine reproductive immunoinfertility: pathogenesis and immunotherapy

“…Targowski ( 79 ) found that an intrauterine infusion of 100 g E. coli LPS increased the number of PMNs found in uterine secretions at 6 and 24 h after treatment in healthy cows. Rashid Dar et al ( 7 ) evaluated the immunomodulatory effect of curcumin 30 M, lipopolysaccharide (LPS), and/or flagellin (100 ng/mL each) on prostaglandin E2 (PGE2) and proinflammatory cytokines (PIC) production using primary bubaline endometrial stromal cells. They discovered that LPS stimulates PGE2 production strongly, but flagellin has a lesser stimulatory impact.…”

“…Antibiotics administered intrauterine reduce uterine leukocytic activity, which could have major consequences in the treatment of metritis if the bacteria involved grow resistant to the antibiotic. Extensive use of antibiotics not only causes antimicrobial drug resistance but is also responsible for the secretion of drug residues in the milk (7). Apart from antibiotics, endometrial necrosis and fibrosis can be caused by overdose or continuous use of a variety of different drugs, such as Lugol's iodine and polyvinylpyrrolidone-iodine (66)(67)(68).…”

“…Reproductive disorders particularly endometritis is one of the major reproductive problems challenging for bovines and antibiotic resistance is further complicating the problem. Immunomodulators have the potential to replace the use of antibiotics against endometritis ( 7 ). The present review aims to summarize the findings on immunoinfertility including its diagnosis, prevention, and control and to overcome its effect by various immunomodulators.…”