MCP-1: Chemoattractant with a role beyond immunity: A review

Yadav, Amita; Saini, Vandana; Arora, Sarika

doi:10.1016/j.cca.2010.07.006

Cited by 414 publications

(332 citation statements)

References 160 publications

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“…Moreover, IDR-1018 had relatively equivalent effects on production of cytokines and MCP-1 by macrophages in vitro, whereas in vivo, IDR-1018 had a greater effect on TNF-a levels, an intermediate effect on MCP-1, and little or no effect on IL-6. The difference between the in vitro and in vivo effects might be explained by macrophages being primarily responsible for TNF-a production in vivo [7], whereas IL-6 is primarily produced by other cell types [36] that are less affected by IDR-1018, and MCP-1 is produced by both macrophages and other cell types [44]. Consistent with this possibility, the relative in vitro cytokine levels in macrophage cell cultures compared with in vivo are highest for TNF-a, intermediate for MCP-1, and lowest for IL-6.…”

Section: Discussionmentioning

confidence: 99%

Immunomodulatory Peptide IDR-1018 Decreases Implant Infection and Preserves Osseointegration

Choe

Narayanan

Gandhi

et al. 2015

Clinical Orthopaedics &Amp; Related Research

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Background Innate defense regulator peptide-1018 (IDR-1018) is a 12-amino acid, synthetic, immunomodulatory host defense peptide that can reduce soft tissue infections and is less likely to induce bacterial resistance than conventional antibiotics. However, IDRs have not been tested on orthopaedic infections and the immunomodulatory effects of IDR-1018 have only been characterized in response to lipopolysacharide, which is exclusively produced by Gram-negative bacteria. Questions/purposes We sought (1) to more fully characterize the immunomodulatory effects of IDR-1018, especially in response to Staphylococcus aureus; and (2) to determine whether IDR-1018 decreases S aureus infection of orthopaedic implants in mice and thereby protects the implants from failure to osseointegrate. Methods In vitro effects of IDR-1018 on S aureus were assessed by determining minimum inhibitory concentrations in bacterial broth without and with supplementation of physiologic ion levels. In vitro effects of IDR-1018 on macrophages were determined by measuring production of monocyte chemoattractant protein-1 (MCP-1) and proinflammatory cytokines by enzyme-linked immunosorbent assay. In vivo effects of IDR-1018 were determined in a murine model of S aureus implant infection by quantitating bacterial burden, macrophage recruitment, MCP-1, proinflammatory cytokines, and osseointegration in nine mice per group on Day 1 postimplantation and 20 mice per group on Day 15 postimplantation. Results IDR-1018 demonstrated antimicrobial activity by directly killing S aureus even in the presence of physiologic ion levels, increasing recruitment of macrophages to the site of infections by 40% (p = 0.036) and accelerating S aureus clearance in vivo (p = 0.008) with a 2.6-fold decrease in bacterial bioburden on Day 7 postimplantation.

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Section: Discussionmentioning

confidence: 99%

Immunomodulatory Peptide IDR-1018 Decreases Implant Infection and Preserves Osseointegration

Choe

Narayanan

Gandhi

et al. 2015

Clinical Orthopaedics &Amp; Related Research

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“…CCL2 (also termed MCP-1 2 for monocyte chemotactic protein-1) is a small cytokine belonging to the CC chemokine family. It participates in monocyte recruitment during infection or under other inflammatory conditions (13). Since it is known that many tumors secrete CCL2, which attracts tumor-associated macrophages that promote tumor growth, angiogenesis, and metastasis (14 -16), this finding has been connected to the effect of FXYD5 on tumorgenicity.…”

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confidence: 99%

FXYD5 Protein Has a Pro-inflammatory Role in Epithelial Cells

Lubarski-Gotliv

Asher

Dada

et al. 2016

Journal of Biological Chemistry

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The FXYD proteins are a family of small membrane proteins that share an invariant four amino acid signature motif F-X-Y-D and act as tissue-specific regulatory subunits of the Na,KATPase. FXYD5 (also termed dysadherin or RIC) is a structurally and functionally unique member of the FXYD family. As other FXYD proteins, FXYD5 specifically interacts with the Na,K-ATPase and alters its kinetics by increasing V max . However, unlike other family members FXYD5 appears to have additional functions, which cannot be readily explained by modulation of transport kinetics. Knockdown of FXYD5 in MDA-MB-231 breast cancer cells largely decreases expression and secretion of the chemokine CCL2 (MCP-1). A related effect has also been observed in renal cell carcinoma cells. The current study aims to further characterize the relationship between the expression of FXYD5 and CCL2 secretion. We demonstrate that transfection of M1 epithelial cell line with FXYD5 largely increases lipopolysaccharide (LPS) stimulated CCL2 mRNA and secretion of the translated protein. We have completed a detailed analysis of the molecular events leading to the above response. Our key findings indicate that FXYD5 generates a late response by increasing the surface expression of the TNF␣ receptor, without affecting its total protein level, or mRNA transcription. LPS administration to mice demonstrates induced secretion of CCL2 and TNF␣ in FXYD5-expressing lung peripheral tissue, which suggests a possible role for FXYD5 in normal epithelia during inflammation.FXYD is a family of type I plasma membrane proteins characterized by the extracellular motif Phe-Xxx-Tyr-Asp. All seven mammalian members of this family specifically interact with the Na,K-ATPase and they have been described to act as tissue specific regulators or auxiliary subunits of the Na,KATPase whose role is to adjust the pump's activity to the cell environment (1). FXYD5 (also termed dysadherin or RIC) is a structurally and functionally unique member of the FXYD family. As other FXYD proteins, FXYD5 specifically interacts with the Na,K-ATPase and alters its kinetics by increasing V max (2, 3). However, in addition to regulating Na,K-ATPase kinetics, FXYD5 appears to have other functions. FXYD5 has been identified as a cancer-associated protein whose expression inhibits E-cadherin and promotes metastasis (4). Clinical studies have demonstrated correlations between the abundance of FXYD5 and the progression of malignancies and survival chances of patients with various human cancers (for review see Ref. 5). Silencing FXYD5 decreases individual and collective cell motility, while its overexpression has the opposite effect (6 -8). In addition, the expression of FXYD5 has been associated with changes in cytoskeletal organization, altered cell shape and impairment of tight and adherence junctions (6 -10). The above observations are consistent with the fact that the extracellular domain of FXYD5 is much longer than that of other FXYD proteins and presumably undergoes excessive O-glycosylation (4, 11).Prev...

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“…It is generally known that immune cells and cytokines are involved in regulating bone turnover (summarised in Nicolaidou et al, 2012). Of particular importance for bone remodelling is CCL2 (also MCP-1), which is associated, for example, with the recruitment of monocytes to areas of bone formation and bone resorption (reviewed in Yadav et al, 2010). Moreover, this QTL reached suggestive LRT values in both A (30.18) and P (26.46).…”

Section: Resultsmentioning

confidence: 99%

Genome-wide QTL mapping results for regional DXA body composition and bone mineral density traits in pigs

Bernau¹,

Kremer-Rücker

Međugorac³

et al. 2017

Arch. Anim. Breed.

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Abstract. In a previous study, genome-wide mapping of quantitative trait loci (QTL) for five body composition traits, three bone mineral traits and live weight was performed using whole-body dual-energy X-ray absorptiometry (DXA) data. Since QTL for bone mineral traits were rare, the current study aimed to clarify whether the mapping results were influenced by the analysed body regions. Thus, the same material (551 pigs) and methods as in the whole-body QTL mapping study were used. However, for evaluation of the DXA scans, we manually defined two body regions: (i) from the last ribs to the pelvis (A) and (ii) including the pelvis and the hind limbs (P). Since live weight was not affected by the regional analysis, it was omitted from the QTL mapping design.Our results show an overall high consistency of mapping results especially for body composition traits. Two thirds of the initial whole-body QTL are significant for both A and P. Possible causes for the still low number of bone mineral QTL and the lower consistency found for these traits are discussed. For body composition traits, the data presented here show high genome-wide Pearson correlations between mapping results that are based on DXA scans with the time-saving "whole-body standard setting" and mapping results for DXA data that were obtained by time-consuming manual definition of the regions of interest. However, our results also suggest that whole-body or regional DXA scans might generally be less suitable for mapping of bone mineral traits in pigs. An analysis of single reference bones could be more useful.

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MCP-1: Chemoattractant with a role beyond immunity: A review

Cited by 414 publications

References 160 publications

Immunomodulatory Peptide IDR-1018 Decreases Implant Infection and Preserves Osseointegration

Immunomodulatory Peptide IDR-1018 Decreases Implant Infection and Preserves Osseointegration

FXYD5 Protein Has a Pro-inflammatory Role in Epithelial Cells

Genome-wide QTL mapping results for regional DXA body composition and bone mineral density traits in pigs

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