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We hypothesized that<jats:italic>Chlamydia<\/jats:italic>major outer membrane protein (MOMP) mediates its disease pathogenesis, and the suppressor of cytokine signaling (SOCS)1 and SOCS3 proteins are mediators of the IL-10 inhibitory actions. Our hypothesis was tested by exposing mouse J774 macrophages to chlamydial stimulants (live<jats:italic>Chlamydia muridarum<\/jats:italic>and MOMP) with and without IL-10. MOMP significantly induced several inflammatory mediators (IL-6, IL-12p40, CCL5, CXCL10), which were dose-dependently inhibited by IL-10. Chlamydial stimulants induced the mRNA gene transcripts and protein expression of SOCS1 and SOCS3, with more SOCS3 expression. Notably, IL-10 reciprocally regulated their expression by reducing SOCS1 and increasing SOCS3. Specific inhibitions of MAPK pathways revealed that p38, JNK, and MEK1\/2 are required for inducing inflammatory mediators as well as SOCS1 and SOCS3. Chlamydial stimulants triggered an M1 pro-inflammatory phenotype evidently by an enhanced nos2 (M1 marker) expression, which was skewed by IL-10 towards a more M2 anti-inflammatory phenotype by the increased expression of mrc1 and arg1 (M2 markers) and the reduced SOCS1\/SOCS3 ratios. Neutralization of endogenously produced IL-10 augmented the secretion of inflammatory mediators, reduced SOCS3 expression, and skewed the chlamydial M1 to an M2 phenotype. Inhibition of proteasome degradation increased TNF but decreased IL-10, CCL5, and CXCL10 secretion by suppressing SOCS1 and SOCS3 expressions and dysregulating their STAT1 and STAT3 transcription factors. Our data show that SOCS1 and SOCS3 are regulators of IL-10 inhibitory actions, and underscore SOCS proteins as therapeutic targets for IL-10 control of inflammation for<jats:italic>Chlamydia<\/jats:italic>and other bacterial inflammatory diseases.<\/jats:p>","DOI":"10.1155\/2020\/7461742","type":"journal-article","created":{"date-parts":[[2020,6,24]],"date-time":"2020-06-24T23:31:43Z","timestamp":1593041503000},"page":"1-29","source":"Crossref","is-referenced-by-count":20,"title":["Suppressors of Cytokine Signaling (SOCS)1 and SOCS3 Proteins Are Mediators of Interleukin-10 Modulation of Inflammatory Responses Induced by<i>Chlamydia muridarum<\/i>and Its Major Outer Membrane Protein (MOMP) in Mouse J774 Macrophages"],"prefix":"10.1155","volume":"2020","author":[{"given":"Skyla A.","family":"Duncan","sequence":"first","affiliation":[{"name":"Center for NanoBiotechnology Research (CNBR), Department of Biological Sciences, Alabama State University, 1627 Harris Way, Montgomery, AL 36104, 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