<i>In Vitro</i>Activation of Murine Peritoneal Macrophages by Monocyte Chemoattractant Protein-1: Upregulation of CD11b, Production of Proinflammatory Cytokines, and the Signal Transduction Pathway

Biswas, Subhra K.; Sodhi, Ajit

doi:10.1089/10799900252982007

Cited by 63 publications

(43 citation statements)

References 56 publications

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“…APCs, such as macrophages, DCs, and B cells produce IL-12, which was originally identified as an NK-stimulatory factor and shown to exhibit considerable antineoplastic activity (39,40). APCs were found to be activated upon the recognition of Ags from apoptotic target cells (41), and both macrophages and DCs secrete large amounts of IL-12 when treated with MCP-1 in vitro (33,42,43). These findings suggest that the recognition of apoptotic tumor cells together with MCP-1 may activate macrophages and DCs, thereby enhancing IL-12 secretion.…”

Section: Discussionmentioning

confidence: 87%

“…3, A and B). Similarly, the numbers of F4/80 or Mac-1 positive cells (32,33) tended to be higher upon tumor rechallenge in mice whose primary tumors had been eradicated with Ad-tk-MCP1. Moreover, the mRNA of IFN-␥ secreted by NK cells (34) became detectable after 30 PCR cycles in the rechallenged tumors of animals whose primary tumors had been eradicated with Adtk-MCP1 and was greatly amplified after 40 PCR cycles (Fig.…”

Section: Recruitment and Activation Of Nk Cells In Rechallenged Tumorsmentioning

confidence: 90%

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Prolonged, NK Cell-Mediated Antitumor Effects of Suicide Gene Therapy Combined with Monocyte Chemoattractant Protein-1 against Hepatocellular Carcinoma

Tsuchiyama

Nakamoto

Sakai

et al. 2007

The Journal of Immunology

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Tumor recurrence rates remain high after curative treatments for hepatocellular carcinoma (HCC). Immunomodulatory agents, including chemokines, are believed to enhance the antitumor effects of tumor cell apoptosis induced by suicide gene therapy. We therefore evaluated the immunomodulatory effects of a bicistronic recombinant adenovirus vector (rAd) expressing both HSV thymidine kinase and MCP-1 on HCC cells. Using an athymic nude mouse model (BALB/c-nu/nu), primary s.c. tumors (HuH7; human HCC cells) were completely eradicated by rAd followed by treatment with ganciclovir. The same animals were subsequently rechallenged with HCC cells, tumor development was monitored, and the recruitment or activation of NK cells was analyzed immunohistochemically or by measuring IFN-γ mRNA expression. Tumor growth was markedly suppressed as compared with that in mice treated with a rAd expressing the HSV thymidine kinase gene alone (p < 0.001). Suppression of tumor growth was associated with the elevation of serum IL-12 and IL-18. During suppression, NK cells were recruited exclusively, and Th1 cytokine gene expression was enhanced in tumor tissues. The antitumor activity, however, was abolished either when the NK cells were inactivated with anti-asialo GM1 Ab or when anti-IL-12 and anti-IL-18 Abs were administered. These results indicate that suicide gene therapy, together with delivery of MCP-1, eradicates HCC cells and exerts prolonged NK cell-mediated antitumor effects in a model of HCC, suggesting a plausible strategy to prevent tumor recurrence.

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Section: Discussionmentioning

confidence: 87%

Section: Recruitment and Activation Of Nk Cells In Rechallenged Tumorsmentioning

confidence: 90%

Prolonged, NK Cell-Mediated Antitumor Effects of Suicide Gene Therapy Combined with Monocyte Chemoattractant Protein-1 against Hepatocellular Carcinoma

Tsuchiyama

Nakamoto

Sakai

et al. 2007

The Journal of Immunology

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“…However, the aP2 promoter used in these experiments to drive transgenic Ccl2 expression is not specific for adipocytes and is also active in macrophages [29]. Since MCP-1 is known to activate macrophages [13,14], it is entirely feasible that the increased recruitment of macrophages into adipose tissue in these studies is facilitated by secretion of MCP-1 and other chemokines/cytokines by constitutively activated macrophages. One of these studies also found that a single intramuscular treatment with a plasmid encoding a human mutant form of Ccl2 (7ND), which dimerises with wild-type MCP-1 and inhibits its activity, was sufficient to reduce insulin resistance in obese db/db mice [27].…”

Section: Discussionmentioning

confidence: 99%

“…Monocyte chemoattractant protein-1 (MCP-1) is a chemokine that is known to affect the accumulation and function of macrophages [12][13][14]. MCP-1 levels are increased in plasma and adipose tissue in mouse models of obesity [15,16], and correlate with the number of CD11b + monocytes in these animals [16].…”

mentioning

confidence: 99%

Monocyte chemoattractant protein-1-induced tissue inflammation is critical for the development of renal injury but not type 2 diabetes in obese db/db mice

et al. 2006

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Aims/hypothesis Tissue macrophage accumulation is thought to induce insulin resistance during obesity and stimulate the progression of diabetic nephropathy. Monocyte chemoattractant protein-1 (MCP-1) is a potent stimulator of macrophage recruitment. It is increased in adipose tissue during obesity and in diabetic kidneys, suggesting that inflammation of these tissues may be MCP-1-dependent. Based on these findings, the aim of this study was to examine whether a deficiency in MCP-1 would alter the development of type 2 diabetes and its renal complications. Materials and methods The role of MCP-1 in the progression of type 2 diabetes and its associated renal injury was assessed in obese db/db mice that were deficient in the gene encoding MCP-1 (Ccl2). Results The incidence and development of type 2 diabetes were similar in Ccl2 +/+ and Ccl2 −/− db/db mice between 8 and 32 weeks of age. Body mass, hyperglycaemia, hyperinsulinaemia, glucose and insulin tolerance, plasma triacylglycerol and serum NEFA were not different between these strains. Pathological changes in epididymal adipose tissue, including increases in macrophage accumulation and Tnfa mRNA and reductions in Adipoq mRNA, were unaffected by the absence of MCP-1. In contrast, kidney macrophage accumulation and the progression of diabetic renal injury (albuminuria, histopathology, renal fibrosis) were substantially reduced in Ccl2 −/− compared with Ccl2 +/+ db/db mice with equivalent diabetes. Conclusions/interpretation Our study demonstrates that MCP-1 promotes type 2 diabetic renal injury but does not influence the development of obesity, insulin resistance or type 2 diabetes in db/db mice. MCP-1 plays a critical role in inflammation of the kidney, but not adipose tissue, during the progression of type 2 diabetes.

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“…However, a large number of highly activated Mac-1 expressing residual microglial cells was scattered throughout the CNS parenchyma in the IFN-␤ KO group, and this was virtually absent in the wt group. Mac-1, also referred to as CD11b/CD18 or CR3, is constitutively expressed on cells of the myeloid macrophage lineage, but is further up-regulated upon activation (40,41). It can bind to several receptors and molecules, such as ICAM-1/2, C3bi, and fibrinogen (42).…”

Section: Discussionmentioning

confidence: 99%

IFN-β Gene Deletion Leads to Augmented and Chronic Demyelinating Experimental Autoimmune Encephalomyelitis

Teige

Treschow

Teige

et al. 2003

The Journal of Immunology

193

190

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Since the basic mechanisms behind the beneficial effects of IFN-β in multiple sclerosis (MS) patients are still obscure, here we have investigated the effects of IFN-β gene disruption on the commonly used animal model for MS, experimental autoimmune encephalomyelitis (EAE). We show that IFN-β knockout (KO) mice are more susceptible to EAE than their wild-type (wt) littermates; they develop more severe and chronic neurological symptoms with more extensive CNS inflammation and demyelination. However, there was no discrepancy observed between wt and KO mice regarding the capacity of T cells to proliferate or produce IFN-γ in response to recall Ag. Consequently, we addressed the effect of IFN-β on encephalitogenic T cell development and the disease initiation phase by passive transfer of autoreactive T cells from KO or wt littermates to both groups of mice. Interestingly, IFN-β KO mice acquired a higher incidence and augmented EAE regardless of the source of T cells. This shows that the anti-inflammatory effect of endogenous IFN-β is predominantly exerted on the effector phase of the disease. Histopathological investigations of CNS in the effector phase revealed an extensive microglia activation and TNF-α production in IFN-β KO mice; this was virtually absent in wt littermates. This coincided with an increase in effector functions of T cells in IFN-β KO mice, as measured by IFN-γ and IL-4 production. We suggest that lack of endogenous IFN-β in CNS leads to augmented microglia activation, resulting in a sustained inflammation, cytokine production, and tissue damage with consequent chronic neurological deficits.

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In VitroActivation of Murine Peritoneal Macrophages by Monocyte Chemoattractant Protein-1: Upregulation of CD11b, Production of Proinflammatory Cytokines, and the Signal Transduction Pathway

Cited by 63 publications

References 56 publications

Prolonged, NK Cell-Mediated Antitumor Effects of Suicide Gene Therapy Combined with Monocyte Chemoattractant Protein-1 against Hepatocellular Carcinoma

Prolonged, NK Cell-Mediated Antitumor Effects of Suicide Gene Therapy Combined with Monocyte Chemoattractant Protein-1 against Hepatocellular Carcinoma

Monocyte chemoattractant protein-1-induced tissue inflammation is critical for the development of renal injury but not type 2 diabetes in obese db/db mice

IFN-β Gene Deletion Leads to Augmented and Chronic Demyelinating Experimental Autoimmune Encephalomyelitis

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