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We examined 104 samples of PD effluent collected during acute peritonitis for correspondence between a broad range of soluble parameters and neutrophil counts. We observed an association between peritoneal IL\u201017 and neutrophil levels. This relationship was evident in effluent samples with low but not high IFN\u2010\u03b3 levels, suggesting a differential effect of IFN\u2010\u03b3 concentration on neutrophil infiltration. Surprisingly, there was no association of neutrophil numbers with the level of CXCL1, a key IL\u201017\u2010induced neutrophil chemoattractant. We investigated therefore the production of CXCL1 by human peritoneal mesothelial cells (HPMCs) under <jats:italic>in vitro<\/jats:italic> conditions mimicking clinical peritonitis. Stimulation of HPMCs with IL\u201017 increased CXCL1 production through induction of transcription factor SP1 and activation of the SP1\u2010binding region of the <jats:italic>CXCL1<\/jats:italic> promoter. These effects were amplified by TNF\u03b1. In contrast, IFN\u2010\u03b3 dose\u2010dependently suppressed IL\u201017\u2010induced SP1 activation and CXCL1 production through a transcriptional mechanism involving STAT1. The SP1\u2010mediated induction of CXCL1 was also observed in HPMCs exposed to PD effluent collected during peritonitis and containing IL\u201017 and TNF\u03b1, but not IFN\u2010\u03b3. Supplementation of the effluent with IFN\u2010\u03b3 led to a dose\u2010dependent activation of STAT1 and a resultant inhibition of SP1\u2010induced <jats:italic>CXCL1<\/jats:italic> expression. Transmesothelial migration of neutrophils <jats:italic>in vitro<\/jats:italic> increased upon stimulation of HPMCs with IL\u201017 and was reduced by IFN\u2010\u03b3. In addition, HPMCs were capable of binding CXCL1 at their apical cell surface. These observations indicate that changes in relative peritoneal concentrations of IL\u201017 and IFN\u2010\u03b3 can differently engage SP1\u2013STAT1, impacting on mesothelial cell transcription of <jats:italic>CXCL1<\/jats:italic>, whose release and binding to HPMC surface may determine optimal neutrophil recruitment and retention during peritonitis. \u00a9 2020 The Authors. <jats:italic>The Journal of Pathology<\/jats:italic> published by John Wiley &amp; Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.<\/jats:p>","DOI":"10.1002\/path.5438","type":"journal-article","created":{"date-parts":[[2020,3,31]],"date-time":"2020-03-31T04:35:23Z","timestamp":1585629323000},"page":"175-186","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Control of neutrophil influx during peritonitis by transcriptional cross\u2010regulation of chemokine <scp>CXCL1<\/scp> by <scp>IL<\/scp>\u201017 and <scp>IFN<\/scp>\u2010\u03b3"],"prefix":"10.1002","volume":"251","author":[{"given":"Rusan A","family":"Catar","sequence":"first","affiliation":[{"name":"Department of Nephrology and Medical Intensive Care Charit\u00e9\u2010Universit\u00e4tsmedizin  Berlin Germany"},{"name":"Berlin Institute of Health  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Medical Intensive Care Charit\u00e9\u2010Universit\u00e4tsmedizin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone M","family":"Cuff","sequence":"additional","affiliation":[{"name":"Division of Infection &amp; 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