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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

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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). PGE2 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 PGE2 production and upregulated IL6 and IL8 genes. Curcumin inhibited the basal and LTA+LPS induced production of PGE2 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 PGE2 and may be an alternate to antimicrobial drugs for the therapeutic management of endometritis.

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Fig. 1
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Availability of data and material

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The work was supported by National Agricultural Science Fund (NASF) on “Synthetic Endometrium: A novel model to study early embryonic development and uterine health in ruminants” (Project Code: OXX03803) and All India Coordinated Research Project (AICRP) on “Nutritional and physiological approaches for enhancing reproductive performance in cattle and buffalo” (Project code: OXX03079). We thank the Director, ICAR-IVRI for facilitating the work. The first author thanks ICAR for providing Junior Research Fellowship.

Funding

The work was supported by National Agricultural Science Fund (NASF) on “Synthetic Endometrium: A novel model to study early embryonic development and uterine health in ruminants” (Project Code: OXX03803) and All India Coordinated Research Project (AICRP) on “Nutritional and physiological approaches for enhancing reproductive performance in cattle and buffalo” (Project code: OXX03079).

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Authors and Affiliations

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

    Ajaz Ali, Rouf Rashid Dar, Sanjay Kumar Singh & Harendra Kumar

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

    Sheikh Firdous Ahmad & Manjit Panigrahi

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

    Sheikh Firdous Ahmad

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

    Manas Kumar Patra

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

    Narayanan Krishnaswamy

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  1. Ajaz Ali
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Correspondence to Sanjay Kumar Singh.

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Ali, A., Dar, R.R., Ahmad, S.F. et al. Curcumin inhibits lipopolysaccharide and lipoteichoic acid-induced expression of proinflammatory cytokines and production of PGE2 in the primary bubaline endometrial stromal cells. Mol Biol Rep 47, 10015–10021 (2020). https://doi.org/10.1007/s11033-020-05961-y

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