Serum-Glucocorticoid Regulated Kinase 1 Regulates Alternatively Activated Macrophage Polarization Contributing to Angiotensin II–Induced Inflammation and Cardiac Fibrosis

Yang, Min; Zheng, Jiao; Miao, Yanjv; Wang, Ying; Cui, Wei; Guo, Jun; Qiu, Siqi; Han, Yalei; Jia, Lixin; Li, Huihua; Cheng, Jizhong; Du, Jie

doi:10.1161/atvbaha.112.248732

Cited by 130 publications

(128 citation statements)

References 51 publications

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“…In fact, few recent studies show different mechanisms of M2 polarization of TAMs involving STAT3 activation (24,25). Thus, we hypothesized that Reg3b might exert its effects on TAMs through activation of STAT3.…”

Section: M2 Tam Polarization Is Reduced In Reg3bmentioning

confidence: 91%

Reg3β Deficiency Impairs Pancreatic Tumor Growth by Skewing Macrophage Polarization

et al. 2013

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The lectin Reg3b provides crucial protection to various tissues against inflammation, a potential risk factor for pancreatic ductal adenocarcinoma. Reg3b is also overexpressed in serum and pancreatic juice from patients with this cancer, but its function in this context remains to be elucidated. In this study, we investigated the role of Reg3b in tumor development in an orthotopic mouse model of pancreatic cancer. Reg3b deletion in mice drastically impaired pancreatic tumor growth, correlating with decreased angiogenesis and increased apoptosis of tumor cells. Moreover, Reg3b deficiency resulted in an alteration of the tumoral immune microenvironment, reflected by a decrease in the M2/M1 ratio of tumor-associated macrophages and an upregulation of CD3 þ cell infiltration. Addition of Reg3b to prestimulated RAW 264.7 or primary macrophages enhanced M2 polarization through the activation of STAT3 signaling pathway. Conditioned media from Reg3b-M2-polarized primary macrophages inhibited apoptosis and prolonged the viability of Panc02 tumor cells. Our studies reveal a novel role for Reg3b as a tumor promoter in pancreatic adenocarcinoma through the regulation of tumor stroma. Thus, inhibition of this protein may be a useful strategy in treatment of pancreatic cancer. Cancer Res; 73(18); 5682-94. Ó2013 AACR.

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Section: M2 Tam Polarization Is Reduced In Reg3bmentioning

confidence: 91%

Reg3β Deficiency Impairs Pancreatic Tumor Growth by Skewing Macrophage Polarization

et al. 2013

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“…These sections were incubated with anti-a-SMA (1:200; SigmaAldrich) and anti-TGF-b (1:500; Abcam) Abs at 4˚C overnight and then incubated with secondary Ab and detected with 3,39-diaminobenzidine. Immunofluorescent staining was performed as described previously (20). …”

Section: Histopathology and Immunohistochemistrymentioning

confidence: 99%

CX3CL1–CX3CR1 Interaction Increases the Population of Ly6C−CX3CR1hi Macrophages Contributing to Unilateral Ureteral Obstruction–Induced Fibrosis

Peng

Zhang

Xiao

et al. 2015

The Journal of Immunology

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Chemokines modulate inflammatory responses that are prerequisites for kidney injury. The specific role of monocyte-associated CX3CR1 and its cognate ligand CX3CL1 in unilateral ureteral obstruction (UUO)–induced kidney injury remains unclear. In this study, we found that UUO caused a CCR2-dependent increase in numbers of Ly6Chi monocytes both in the blood and kidneys and of Ly6C−CX3CR1+ macrophages in the obstructed kidneys of mice. Using CX3CR1gfp/+ knockin mice, we observed a rapid conversion of infiltrating proinflammatory Ly6C+CX3CR11o monocytes/macrophages to anti-inflammatory Ly6C−CX3CR1hi macrophages. CX3CR1 deficiency affected neither monocyte trafficking nor macrophage differentiation in vivo upon renal obstruction, but CX3CR1 expression in monocytes and macrophages was required for increases in fibrosis in the obstructed kidneys. Mechanistically, CX3CL1–CX3CR1 interaction increases Ly6C−CX3CR1hi macrophage survival within the obstructed kidneys. Therefore, CX3CL1 and CX3CR1 may represent attractive therapeutic targets in obstructive nephropathy.

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“…During the early phase of cardiac inflammation, it is likely that the M1 macrophages are recruited to and infiltrate the heart expressing pro-inflammatory cytokines and mediate cardiac fibrosis [64]. The microenvironment of the heart may cause differentiation of M1 and/or M2 macrophages in the development of fibrosis [65]. In the context of our study described above M1 MAC387 + macrophages traffic to the heart with the development of AIDS as potential anti-viral agents that initiate the inflammatory process, while CD163 + M2 macrophages are recruited from the monocyte pool that differentiate and may begin the process of fibrosis.…”

Section: Macrophage Infiltration and Pathology In The Heart During Simentioning

confidence: 99%

“…Additionally, blocking macrophage traffic to the heart reduced the frequency and severity of cardiac fibrosis (Walker, unpublished). This suggests that blocking traffic of macrophages directly can decrease the number of M1 macrophages that begin the inflammatory process, as well as decrease M2 macrophages that play a role in cardiac fibrosis [65].…”

Section: Macrophage Infiltration and Pathology In The Heart During Simentioning

confidence: 99%

Macrophage Polarization in AIDS: Dynamic Interface between Anti-Viral and Anti-Inflammatory Macrophages during Acute and Chronic Infection

Burdo

Walker

Williams

2015

J Clin Cell Immunol

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Monocyte and macrophage inflammation in parenchymal tissues during acute and chronic HIV and SIV infection plays a role in early anti-viral immune responses and later in restorative responses. Macrophage polarization is observed in such responses in the central nervous system (CNS) and the heart and cardiac vessels that suggest early responses are M1 type antiviral responses, and later responses favor M2 restorative responses. Macrophage polarization is unique to different tissues and is likely dictated as much by the local microenvironment as well as other inflammatory cells involved in the viral responses. Such polarization is found in HIV infected humans, and the SIV infected animal model of AIDS, and occurs even with effective anti-retroviral therapy. Therapies that directly target macrophage polarization in HIV infection have recently been implemented, as have therapies to directly block traffic and accumulation of macrophages in tissues.

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Serum-Glucocorticoid Regulated Kinase 1 Regulates Alternatively Activated Macrophage Polarization Contributing to Angiotensin II–Induced Inflammation and Cardiac Fibrosis

Abstract: SGK1 may play an important role in macrophage recruitment and M2 macrophage activation by activating the STAT3 pathway, which leads to angiotensin II-induced cardiac fibrosis.

Cited by 130 publications

References 51 publications

Reg3β Deficiency Impairs Pancreatic Tumor Growth by Skewing Macrophage Polarization

Reg3β Deficiency Impairs Pancreatic Tumor Growth by Skewing Macrophage Polarization

CX3CL1–CX3CR1 Interaction Increases the Population of Ly6C−CX3CR1hi Macrophages Contributing to Unilateral Ureteral Obstruction–Induced Fibrosis

Macrophage Polarization in AIDS: Dynamic Interface between Anti-Viral and Anti-Inflammatory Macrophages during Acute and Chronic Infection

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