Rabbit Anti-Mouse CCL9 Polyclonal antibody

P-selectin glycoprotein ligand 1 (SELPLG/PSGL-1) is an inflammatory molecule that is functionally related to immune cell differentiation and leukocyte mobilization. However, the role of PSGL-1 in tumor development remains unknown. Therefore, this study investigates the mechanistic role of PSGL-1 in the development of intestinal tumors in colorectal cancer. Apc(Min/+) mice are highly susceptible to spontaneous intestinal adenoma formation, and were crossbred with PSGL1-null mice to generate compound transgenic mice with a Apc(Min/+); PSGL-1(-/)-genotype. The incidence and pathologic features of the intestinal tumors were compared between the Apc(Min/+) mice and Apc(Min/+); PSGL-1(-/)-mice. Importantly, PSGL-1-deficient mice showed increased susceptibility to develop intestinal tumors and accelerated tumor growth. Mechanistically, increased production of the mouse chemokine ligand 9 (CCL9/MIP-1 gamma) was found in the PSGL-1-deficient mice, and the macrophages are likely the major source of macrophage inflammatory protein-1 gamma (MIP-1 gamma). Studies in vitro demonstrated that macrophage-derived MIP-1g promoted colorectal cancer tumor cell growth through activating NF kappa B signaling. Conversely, restoration of the PSGL-1 signaling via bone marrow transplantation reduced MIP-1g production and attenuated the ability of Apc(Min/+); PSGL-1(-/)-mice to generate intestinal tumors. In human colorectal cancer clinical specimens, the presence of PSGL-1-positive cells was associated with a favorable tumornode-metastasis staging and decreased lymph node metastasis. Implications: PSGL-1 deficiency and inflammation render intestinal tissue more vulnerable to develop colorectal tumors through a MIP-1g/NF kappa B signaling axis. (C) 2017 AACR.

In this study, we examined the combined effect of aging and myocardial infarction on left ventricular remodeling, focusing on matrix metalloproteinase (MMP)-9-dependent mechanisms. We enrolled 55 C57BL/6J wild type (WT) and 85 MMP-9 Null (Null) mice of both sexes at 11-36 months of age and evaluated their response at Day 7 post-myocardial infarction. Plasma MMP-9 levels positively linked to age in WT mice (r =.46, p =.001). MMP-9 deletion improved survival (76% for WT vs 88% for Null, p =.021). Post-myocardial infarction, there was a progressive increase in left ventricular dilation with age in WT but not in Null mice. By inflammatory gene array analysis, WT mice showed linear age-dependent increases in three different proinflammatory genes (C3, CCl4, and CX3CL1; all p <.05), whereas Null mice showed increases in three proinflammatory genes (CCL5, CCL9, and CXCL4; all p <.05) and seven anti-inflammatory genes (CCL1, CCL6, CCR1, IL11, IL1r2, IL8rb, and Mif; all p <.05). Compared with WT, macrophages isolated from Null left ventricle infarct demonstrated enhanced expression of anti-inflammatory M2 markers CD163, MRC1, TGF-beta 1, and YM1 (all p <.05), without affecting proinflammatory M1 markers. In conclusion, MMP-9 deletion stimulated anti-inflammatory polarization of macrophages to attenuate left ventricle dysfunction in the aging post-myocardial infarction.