Curcumin inhibits lipopolysaccharide and lipoteichoic acid-induced expression of proinflammatory cytokines and productio

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Curcumin inhibits lipopolysaccharide and lipoteichoic acid‑induced expression of proinflammatory cytokines and production of ­PGE2 in the primary bubaline endometrial stromal cells Ajaz Ali1 · Rouf Rashid Dar1 · Sheikh Firdous Ahmad2,3   · Sanjay Kumar Singh1 · Manas Kumar Patra4 · Manjit Panigrahi2 · Harendra Kumar1 · Narayanan Krishnaswamy5 Received: 6 June 2020 / Accepted: 29 October 2020 © Springer Nature B.V. 2020

Abstract Infection of the uterus with Gram-positive Trueperella pyogenes and Gram-negative Escherichia coli is a common cause of postpartum endometritis in the cattle and buffalo and the condition is treated with antimicrobial drugs. The presence of drug residues in the milk and development of resistant bacteria necessitate the evaluation of alternate therapies for endometritis. Accordingly, we tested the immunomodulatory effect of curcumin in the bubaline endometrial stromal cells after treatment with the lipoteichoic acid (LTA) of Gram-positive Staphylococcus aureus and lipopolysaccharide (LPS) of Gram-negative E. coli that activate toll-like receptors (TLR-2 and TLR-4, respectively). Confluent primary culture of endometrial stromal cells was treated with LTA (1 µg/mL) and/or LPS (0.1 µg/mL), in the presence or absence of curcumin (30 µM for 24 h). P ­ GE2 was assayed in the supernatant and the relative expression of proinflammatory cytokines (PICs) (IL1B, IL6, IL8 and TNFA) transcripts were quantified using real-time PCR. LTA was not effective in stimulating ­PGE2 production or upregulating the PIC expression except IL8. LTA+LPS increased P ­ GE2 production and upregulated IL6 and IL8 genes. Curcumin inhibited the basal and LTA+LPS induced production of P ­ GE2 and upregulation of PIC production. It was apparent that LPS, but not LTA, is a potent stimulator of ­PGE2 from the bubaline endometrial stromal cells. Curcumin downregulated the expression of LPS and/or LTA induced PICs and P ­ GE2 and may be an alternate to antimicrobial drugs for the therapeutic management of endometritis. Keywords  Buffalo · Curcumin · Endometritis · In vitro · LTA · LPS

Introduction

* Sanjay Kumar Singh [email protected]; [email protected] 1



Division of Animal Reproduction, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, UP 243122, India

2



Division of Animal Genetics, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, UP 243122, India

3

Animal Genetics and Breeding, ICAR-National Research Centre on Pig, Rani, Guwahati, Assam 781131, India

4

Livestock Production and Management Section, ICAR-Indian Veterinary Research Institute Izatnagar, Bareilly, UP 243122, India

5

ICAR-Indian Veterinary Research Institute, Hebbal Campus, Bengaluru 560024, India





Bacterial contamination of the uterus during the first three weeks of postpartum (PP) in the dairy cattle and buffalo is considered inevitable [1, 2]. The development of PP endometritis is an outcome of complex interactions between the innate immunity of the host, the load of pathogenic ba