IL10 is a potent modulator of IL1-mediated inflammation in bovine endometrial explants

CONTEXT: Bovine uterine inflammation impairs fertility, animal welfare and economics. Balanced regulation of interleukin-1 family proteins is crucial to resolve endometrial inflammation. AIM: mRNA expression of interleukin 1B (IL1B) and its receptor antagonist (IL1RA) was examined in bovine endometrial explants. METHODS: Endometrial explants from 26 cows were incubated with heat-inactivated pathogenic Escherichia coli, opportunistic Bacillus pumilus or commensal and potentially protective Lactobacillus buchneri (3, 14 and 24 h) and with cytokines (24 h; IL1B, IL17A, IL10). mRNA expression of IL1B and IL1RA was quantified via reverse-transcription quantitative polymerase chain reaction (RT-qPCR) and mixed effects models were used for statistical analysis. KEY RESULTS: IL1B mRNA expression increased after bacterial challenge at all timepoints (P < 0.001). IL1RA mRNA expression increased after Escherichia coli and Bacillus pumilus exposure only at 3 h, but after Lactobacillus buchneri at 14 and 24 h (P < 0.010). A pro-inflammatory shift of the IL1RA:IL1B ratio was detected at all timepoints and for all bacterial challenges (P < 0.020). Stimulation with IL10 reduced IL1B and IL1RA mRNA expression and shifted the IL1RA:IL1B ratio in an anti-inflammatory direction (P < 0.001). CONCLUSION: This study confirmed explant culture as a suitable model for analyzing inflammatory regulation in the bovine endometrium and identified IL10 as a potent modulator of endometrial IL1B and IL1RA. IMPLICATIONS: Not only Escherichia coli and Bacillus pumilus, but also unexpectedly Lactobacillus buchneri, induced initial pro-inflammatory mRNA expression patterns to be different depending on culture duration. This highlights the need for further research on pathogenic and opportunistic versus potentially protective bacteria in bovine uterine health.