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Innate Immune System in Cardiovascular Diseases
Published in Shyam S. Bansal, Immune Cells, Inflammation, and Cardiovascular Diseases, 2022
Benjamin J. Kopecky, Kory J. Lavine
The innate immune system is implicated in coronary development as well as in the progression and stabilization of atherosclerosis [18, 87]. CCR2− macrophages are essential mediators of coronary development [35], and they aid in remodeling and maturation of the coronary vasculature through insulin-like growth factors 1 and 2 [35]. On the other hand, macrophages (CCR2+ predominantly) are essential to vascular inflammation and the progression of atherosclerosis [88]. Atherosclerosis is characterized by low-grade inflammation marked by macrophage-derived cytokines (IL-1β, IL-6, TNF) [88]. The Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS) trial enrolled patients with high-risk coronary artery disease to receive IL-1β blockade, and the results showed a significant reduction in ischemic and cardiovascular events [89].
Nuclear Factor Kappa-B: Bridging Inflammation and Cancer
Published in Surinder K. Batra, Moorthy P. Ponnusamy, Gene Regulation and Therapeutics for Cancer, 2021
Mohammad Aslam Khan, Girijesh Kumar Patel, Haseeb Zubair, Nikhil Tyagi, Shafquat Azim, Seema Singh, Aamir Ahmad, Ajay Pratap Singh
Genomic instability and uncontrolled proliferative signaling is more relevant to the initiation of tumorigenesis but a majority of cancer-associated deaths are due to metastases of tumor cells [31]. Tumor cells undergo cellular transition i.e. epithelial to mesenchymal transition (EMT), and this process is considered critical for the tumor cells to migrate from primary sites to other (metastatic) sites in the body. Inflammatory cytokines such as IL-6, TNF and IL-1 induce EMT by activating NF-κB and STAT3 signaling [36–38]. IL-4-activated tumor associated macrophages (TAMs) as well as CCR1+ immature myeloid cells secrete matrix degrading enzymes which help in tumor cell invasion [39, 40]. Moreover, CCL-2 mediated recruitment of Gi1+ and CCR2+ inflammatory monocytes helps in the metastases of breast cancer cells and inhibition of CCL2-CCR2 signaling axis increases survival of tumor bearing mice [41]. Thus, prolonged inflammation helps in the cellular transformation and early events of tumorigenesis, whereas inflammatory tumor microenvironment induces tumor aggressiveness in the later events.
Chemokines and Chemokine Receptor Interactions and Functions
Published in Thomas R. O’Brien, Chemokine Receptors and AIDS, 2019
Philip L. Shields, David H. Adams
Chemokines play a significant role in atherogenesis (reviewed in references 94 and 95). Immune cells infiltrate vascular lesions from the earliest stages and the intimal fatty streak is characterized by the presence of T lymphocytes and macrophages, which differentiate into foam cells after ingesting lipoprotein particles. Given the polyclonal nature of the T cell infiltrate, the presence of T cells in atheromatous plaques is due to active recruitment of these cells rather than clonal antigen mediated expansion in situ (96, 97). Several chemokines, including MCP-1, MCP-4, RANTES, PARC, and ELC, are expressed within atherosclerotic plaques and have been implicated in the recruitment of mononuclear cells (98, 99). Animal models provide direct evidence of a role for chemokines in the pathogenesis of atherosclerosis because over expression of MCP-1 accelerates atheroma development (100, 101), whereas mice lacking the MCP-1 receptor CCR2 show reduced atheroma formation (102). In human studies, CCR2 expression is increased on monocytes in hypercholesterolemic patients compared with normocholesterolemic controls suggesting a mechanism for monocyte recruitment to the vessel wall during atherogenesis (103).
Endotoxin-induced cytokine, chemokine and white blood cell profiles of variable stress-responding sheep
Published in Stress, 2021
D. Naylor, A. Sharma, Z. Li, G. Monteith, B. A. Mallard, R. Bergeron, C. Baes, N. A. Karrow
Serum chemokines were also measured in this study because they are directly responsible for mediating immune cell trafficking and positioning in tissues during the immune response (Sokol & Luster, 2015). All chemokines measured in this study, except IL-8, demonstrated an increase at 4 h post-LPS challenge, but differences among the stress response groups at 4 h were only evident for CCL2 (HSR, MSR > LSR). CCL2 binds to chemokine receptor CCR2 with high affinity, leading to the recruitment of macrophages and monocytes (Deshmane et al., 2009), but it has also been found to enhance the inflammatory response of macrophages (Carson et al., 2017). In this study, HSR and MSR had greater production of CCL2 and inflammatory responses than LSR. Whether this is partially a result of higher serum CCL2 concentrations augmenting the inflammatory responses of specific immune cells in these sheep was not established in this study.
Microglia as therapeutic targets after neurological injury: strategy for cell therapy
Published in Expert Opinion on Therapeutic Targets, 2021
M. Collins Scott, Supinder S. Bedi, Scott D. Olson, Candice M. Sears, Charles S. Cox
However, the effects of these peripheral myeloid cells can be detrimental to the process of neuroinflammation as well. Their depletion can attenuate the neuroinflammatory response. Makinde et al. demonstrated that non-classical monocytes recruit neutrophils to the site of injury. Depletion of non-classical monocytes prior to CCI-injury decreased recruitment of neutrophils; this cell depletion reduced cerebral edema as well [114]. Conversely, our lab has shown the consequences of the depletion of peripheral M/M in blunt TBI. Prior to controlled-cortical impact or sham injury, rats were depleted of M/M with clodronate-liposomes. Pre-injury M/M depletion decreased detectable brain microglia and increased BBB damage and permeability in the CCI group [8]. Morganti et al. found that direct antagonism of CCR2 decreased recruitment of macrophages in the hippocampus after CCI in mice. This decrease in macrophage accumulation correlated with decreased expression of NADPH oxidase and decreased cognitive dysfunction after CCI-injury [106]. These and other results show that when targeting microglia to attenuate detrimental neuroinflammation, other myeloid cells have to be considered.
Chemokine C-C motif ligand 2 suppressed the growth of human brain astrocytes under Ischemic/hypoxic conditions via regulating ERK1/2 pathway
Published in Brain Injury, 2020
Min Yu, Ni Zheng, Dudu Jiang, Lijing Wang, Qing Zhan, Jiangmin Zhao
The chemokine C-C motif ligand 2 (CCL2), also known as monocyte-chemotactic protein-1 (MCP-1), is a key regulator of inflammation following injury to the CNS (9). CCL2 binds to the chemokine receptor type 2 (CCR2) and is mainly expressed in astrocytes in neuroinflammation (10). CCL2 disrupts integrity of cultured brain microvascular endothelial cells (11) which form the basis of the blood-brain barrier (BBB). CCL2 is secreted from astrocyte end feet and is responsible, in part, for the loss of BBB properties (12). The CCL2/CCR2 pathway has been reported as a potential therapeutic target to decrease inflammation in the CNS (13). Tumor necrosis factor-alpha (TNF-α) induces the release of CCL2 through the ERK signaling pathway (14,15). However, the molecular network underlying CCL2 activity in human brain astrocytes under ischemic/hypoxic conditions remains unclear.