title: LPS converts Gr-1(+)CD115(+) myeloid-derived suppressor cells from M2 to M1 via P38 MAPK.
abstract: Myeloid-derived suppressor cells (MDSCs) are heterogeneous populations of immature myeloid cells with strong immunosuppressive function, and play a critical role in the immune evasion of cancer. A subset of MDSCs share many similar characteristics with tumor-associated macrophages (TAMs), but it is largely unclear whether MDSCs also have M1/M2 type polarization in tumor microenvironments. In the present study, we found that Gr-1(+)CD115(+) monocytes in tumor-bearing mice exhibited M2 characteristics with significantly lower expression of iNOS and higher expression of Arginase I. Immunofluorescence staining showed that Gr-1(+)CD115(+) monocytes in tumor sites from LPS-injected mice had a higher expression of iNOS. Similarly, in vitro experiments displayed that LPS-treated Gr-1(+)CD115(+) cells expressed higher levels of iNOS, IL-6, TNF, IL-12, and IL-10 compared with those in non-treated Gr-1(+)CD115(+) monocytes. Extensive study showed that LPS-treated Gr-1(+)CD115(+) monocytes had less ability to convert the CD4(+)CD25(-)cells into CD4(+)CD25(+) Tregs, and also had less suppressive function on CD4(+)CD25(-) conventional T cells. LLC tumors in LPS-injected mice grew significantly slower than those in non-LPS-injected mice. Further experiments suggested that LPS may function through the P38 MAPK signaling pathway to increase the expression of iNOS, and of MyD88 independently. Thus, we can get conclusion that Gr-1(+)CD115(+) monocytes in tumor-bearing mice show M2 type characteristics and LPS can skew this M2 type cells into M1 type through the P38 MAPK pathway and lead to inhibition of the suppressive function of Gr-1(+)CD115(+) monocytes. It suggests that LPS or its analogs may be potential drugs for tumor treatment, inflammation induced by LPS or other components of bacterium or virus may be benefit to the inhibition of tumor cell growth in vivo.
authors.affiliation: Institutes of Biology and Medical Sciences, Soochow University, 199 Ren-Ai Road, Suzhou 215123, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Institutes of Biology and Medical Sciences, Soochow University, 199 Ren-Ai Road, Suzhou 215123, People's Republic of China.
authors.forename: Ruihua
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Institutes of Biology and Medical Sciences, Soochow University, 199 Ren-Ai Road, Suzhou 215123, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: Xia
authors.affiliation: Institutes of Biology and Medical Sciences, Soochow University, 199 Ren-Ai Road, Suzhou 215123, People's Republic of China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zou
authors.affiliation: Institutes of Biology and Medical Sciences, Soochow University, 199 Ren-Ai Road, Suzhou 215123, People's Republic of China.
authors.forename: Anfei
authors.initials: A
authors.lastname: Huang
authors.affiliation: Institutes of Biology and Medical Sciences, Soochow University, 199 Ren-Ai Road, Suzhou 215123, People's Republic of China. Electronic address: sdxiong@suda.edu.cn.
authors.forename: Sidong
authors.initials: S
authors.lastname: Xiong
authors.affiliation: Institutes of Biology and Medical Sciences, Soochow University, 199 Ren-Ai Road, Suzhou 215123, People's Republic of China. Electronic address: j_pzhang@suda.edu.cn.
authors.forename: Jinping
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001119:Arginase / Q000235:genetics / Q000378:metabolism; D018827:Carcinoma, Lewis Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D007108:Immune Tolerance; D008070:Lipopolysaccharides / Q000494:pharmacology*; D020935:MAP Kinase Signaling System; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000145:classification / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000032:analysis*; D019707:Receptors, Chemokine / Q000032:analysis*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: C503133:Gr-1 protein, mouse; D008070:Lipopolysaccharides; D019707:Receptors, Chemokine; D019001:Nitric Oxide Synthase; D016186:Receptor, Macrophage Colony-Stimulating Factor; D048051:p38 Mitogen-Activated Protein Kinases; D001119:Arginase