Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The small inducible gene (SIG) family encodes related proteins that are involved in the overlapping processes of coagulation, inflammation, immune response, and wound repair. This family contains two branches, termed CXC and CC, which are distinguished by whether or not the first two of four conserved cysteine residues are separated by an additional amino acid residue. All of the CXC SIGs map to chromosome 4, including those encoding beta-thromboglobulin (beta TG) and platelet factor 4 (PF4), both of which are expressed by megakaryocytes in a tissue-specific fashion. Both of these latter two genes have been previously reported to be duplicated, there being a PF4 and a PF4alt gene, and a beta TG1 and beta TG2 gene. We now show by pulse-field gel electrophoresis (PFGE) that the beta TG genes are closely linked to the PF4 genes and to other previously mapped CXC SIGs, namely IL8 (encoding interleukin-8), GRO1 (encoding a cytokine also called melanoma growth-stimulatory activity), and two related genes GRO2 and GRO3, on a single 700-kb Sfil fragment localized to chromosome bands 4q12-q13. The only CXC SIG not linked to this cluster is that encoding gamma-interferon-induced 10-Kd protein (INP10), which has been previously localized to 4q21. Analysis of lambda genomic clones demonstrate that the beta TG1 and PF4 genes are separated by less than 7 kb, and the beta TG2 and PF4alt genes by approximately 5 kb. Within each beta TG/PF4 duplication, the beta TG-like gene is upstream of its linked PF4-like gene. Thus, the beta TG/PF4 genes appear to form a close-linked complex expressed in a megakaryocyte-specific fashion. Further genomic studies may provide additional insights into the regulation of the tissue-specific expression of the beta TG/PF4 gene complex, while further analysis of the linked CXC SIG cytokine family may provide further understanding of their evolutionary history.
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PMID:Genes for beta-thromboglobulin and platelet factor 4 are closely linked and form part of a cluster of related genes on chromosome 4. 131 86

Platelet factor-4 (PF-4)/CXCL4 was the first chemokine described to inhibit neovascularization. Here, the product of the nonallelic variant gene of CXCL4, PF-4var1/PF-4alt, designated CXCL4L1, was isolated for the first time from thrombin-stimulated human platelets and purified to homogeneity. Although secreted CXCL4 and CXCL4L1 differ in only three amino acids, CXCL4L1 was more potent in inhibiting chemotaxis of human microvascular endothelial cells toward interleukin-8 (IL-8)/CXCL8 or basic fibroblast growth factor (bFGF). In vivo, CXCL4L1 was also more effective than CXCL4 in inhibiting bFGF-induced angiogenesis in rat corneas. Thus, activated platelets release CXCL4L1, a potent regulator of endothelial cell biology, which affects angiogenesis and vascular diseases.
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PMID:Platelets release CXCL4L1, a nonallelic variant of the chemokine platelet factor-4/CXCL4 and potent inhibitor of angiogenesis. 1545 74

Chemokines influence tumor progression through regulation of leukocyte chemotaxis, angiogenesis, and metastasis. In this study, the regulated expression of angiogenic (stromal cell-derived factor [SDF]-1/CXCL12 and interleukin [IL]-8/CXCL8) and angiostatic (platelet factor [PF]-4var/CXCL4L1 and inducible protein [IP-10]/CXCL10) chemokines was examined in human colorectal and esophageal cancer. In HCT 116 and HCT-8 colorectal adenocarcinoma cells, the production of IL-8 immunoreactivity was up-regulated by IL-1beta, tumor necrosis factor (TNF)-alpha, the toll-like receptor (TLR) ligands double-stranded RNA and peptidoglycan and phorbol ester. Increased PF-4 and synergistic IL-8 and IP-10 induction in carcinoma cells after stimulation with IL-1beta plus TNF-alpha or interferon-gamma was demonstrated by enzyme-linked immunosorbent assay, quantitative reverse transcriptase polymerase chain reaction, or immunocytochemistry. In addition, IL-8 from HT-29 colorectal adenocarcinoma cells was molecularly identified as intact chemokine, as well as NH(2)-terminally truncated, more active IL-8(6-77). The presence of PF-4var, SDF-1, and vascular endothelial growth factor (VEGF) was evidenced by immunohistochemistry in surgical samples from 51 patients operated on for colon adenocarcinoma (AC), esophageal AC, or esophageal squamous cell carcinoma (SCC). PF-4var was strongly detected in colorectal cancer, whereas its expression in esophageal cancer was rather weak. Staining for SDF-1 was almost negative in esophageal SCC, whereas a more intense and frequent staining was observed in AC of the esophagus and colon. Staining for VEGF was moderately to strongly positive in all 3 types of cancer, although less prominent in esophageal AC. The heterogenous expression of angiogenic (IL-8, SDF-1) as well as angiostatic (IP-10, PF-4var) chemokines not only within the tumor and between the different cases but also between the different tumor cell types may indicate a distinct role of the various chemokines in the complex process of tumor development.
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PMID:Expression of angiostatic platelet factor-4var/CXCL4L1 counterbalances angiogenic impulses of vascular endothelial growth factor, interleukin-8/CXCL8, and stromal cell-derived factor 1/CXCL12 in esophageal and colorectal cancer. 2033 99

Inflammation represents a fundamental aspect of the healing process. Besides their primary role in hemostasis, platelets play an active role in the immunological and inflammatory aspect of tissue healing. Indeed , they can be directly involved in the inflammatory response by the production and release of several inflammatory mediators, including a variety of cytokines, such as TGF-beta, IL-1 beta, CD40L, and chemokines, such as CXCL7, CXCL4, CXCL4L1, CCl5, CXCL1, CXCL8, CXCL5, CXCL12, CCL2, CCL3. Platelet are not only a source of several chemokine involved in the inflammatory response and tissue healing, but they also express chemokine receptors, in particular CCR1 CCR3 CCR4 and CXCR4, thus being able to being able to regulate the inflammatory response associated to the healing process. However, this local inflammation must be taken under control, and platelets can prevent the excess of leukocytes recruitment by anti-inflammatory cytokines, such as TGF-beta. For this biological properties of platelets, platelet rich plasma therapy (PRP) is considered an innovative and promising approach that has been extended to many field of medicine, ranging from non-union defects, bone fractures, spinal fusion, bone implant and osteointegration, joint arthroplasty, to the treatment of several traumatic or degenerative pathologies of tendons, cartilage and ligaments.
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PMID:Platelet rich plasma therapy: inflammatory molecules involved in tissue healing. 2364 97

Upon inflammation, circulating monocytes leave the bloodstream and migrate into the tissues, where they differentiate after exposure to various growth factors, cytokines or infectious agents. The best defined macrophage polarization types are M1 and M2. However, the platelet-derived CXC chemokine CXCL4 induces the polarization of macrophages into a unique phenotype. In this study, we compared the effect of CXCL4 and its variant CXCL4L1 on the differentiation of monocytes into macrophages and into immature monocyte-derived dendritic cells (iMDDC). Differently to M-CSF and CXCL4, CXCL4L1 is not a survival factor for monocytes. Moreover, the expression of the chemokine receptors CCR2, CCR5 and CXCR3 was significantly higher on CXCL4L1-treated monocytes compared to M-CSF- and CXCL4-stimulated monocytes. IL-1 receptor antagonist (IL-1RN) expression was upregulated by CXCL4 and downregulated by CXCL4L1, respectively, whereas both chemokines reduced the expression of the mannose receptor (MRC). Furthermore, through activation of CXCR3, CXCL4L1-stimulated monocytes released significantly higher amounts of CCL2 and CXCL8 compared to CXCL4-treated monocytes, indicating more pronounced inflammatory traits for CXCL4L1. In contrast, in CXCL4L1-treated monocytes, the production of CCL22 was lower. Compared to iMDDC generated in the presence of CXCL4L1, CXCL4-treated iMDDC showed an enhanced phagocytic capacity and downregulation of expression of certain surface markers (e.g. CD1a) and specific enzymes (e.g. MMP-9 and MMP-12). CXCL4 and CXCL4L1 did not affect the chemokine receptor expression on iMDDC and cytokine production (CCL2, CCL18, CCL22, CXCL8, IL-10) by CXCL4- or CXCL4L1-differentiated iMDDC was similar. We can conclude that both CXCL4 and CXCL4L1 exert a direct effect on monocytes and iMDDC. However, the resulting phenotypes are different, which suggests a unique role for the two CXCL4 variants in physiology and/or pathology.
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PMID:CXCL4 and CXCL4L1 Differentially Affect Monocyte Survival and Dendritic Cell Differentiation and Phagocytosis. 2782 99