Disease relevance of Ccl4

• Increased expression of MIP-1 alpha and MIP-1 beta mRNAs in the brain correlates spatially and temporally with the spongiform neurodegeneration induced by a murine oncornavirus [1].
• Novel immunotherapy for peritoneal dissemination of murine colon cancer with macrophage inflammatory protein-1beta mediated by a tumor-specific vector, HVJ cationic liposomes [2].
• Injection of hemagglutinating virus of Japan (HVJ) cationic liposomes-MIP-1beta into subcutaneous tumor masses resulted in local expression of MIP-1beta and local accumulation of CD4(+) T lymphocytes [2].
• Med., 1977, 121 (4), 401-402--The femoral CFU-S of mice were reduced when CCL4 was administered in doses which produced toxic hepatitis, but it was not statistically significant [3].

High impact information on Ccl4

• Pathogenicity was associated with T cell production of the macrophage-attracting chemokines CCL3 and CCL4 [4].
• B cells and professional APCs recruit regulatory T cells via CCL4 [5].
• This suggested that the recruitment of regulatory T cells to B cells and APCs by CCL4 plays a central role in the normal initiation of T cell and humoral responses, and failure to do this leads to autoimmune activation [5].
• Among these, CCL4 was the most potent chemoattractant of a CD4+CD25+ T cell population, which is a characteristic phenotype of regulatory T cells [5].
• In addition, we identify macrophage inflammatory protein-1beta as a novel hypoxia-induced neutrophil survival factor [6].

Biological context of Ccl4

• Induction of both MIP-1 alpha and MIP-1 beta by PA was associated with transcriptional activation and mRNA stabilization, suggesting a dual molecular mechanism of control [7].
• A synthetic oligonucleotide probe pool corresponding to the NH2-terminal amino acid sequence of MIP-1 beta was used to isolate a cDNA clone containing its coding sequence [8].
• The increased CCR expression correlates with enhanced in vitro chemotaxis response to MIP-1beta (CCL4) [9].
• In contrast, PGE1 inhibits LPS-induced JE, MIP-1 alpha, and MIP-1 beta mRNA expression and this inhibition is partially dependent on a cAMP-mediated pathway of signal transduction [10].
• The following end points were assessed: i) GSIR; ii) rates of apoptosis; and iii) gene expression for iNOS, IRF-1 and inducible protein (IP)-10, monocyte chemoattractive protein (MCP)-1, macrophage inflammatory protein-1alpha, and macrophage inflammatory protein-1beta [11].

Anatomical context of Ccl4

• We demonstrate that PA is a potent activator of the inflammatory chemokines MIP (macrophage inflammatory protein)-1 alpha and MIP-1 beta (MIPs) mRNA expression in mouse macrophages in a dose- and time-dependent fashion and through a de novo protein synthesis-dependent process [7].
• Finally, the expression of these new receptors appears to have an effect on activation and degranulation because MIP-1beta (CCL4) and TCA-3 (CCL1) induce significant levels of LTC4 from elicited eosinophils [12].
• We described previously the inhibitory effect of PGE(2) on the expression and release of the inflammatory chemokines CCL3 and CCL4 from activated dendritic cells [13].
• Instead, the lower early expression of the neutrophil chemoattractants MIP-1 beta and MIP-2 in the lungs of beige mice tends to suggest that the enhanced susceptibility of these mice to M. avium infection may be due in part to defective recruitment of neutrophils or other cells responsive to these specific chemokines [14].
• This inhibition is not specific to MIP-1 alpha in that expression of MIP-1 beta, a related molecule that does not exhibit potent stem cell inhibitory properties, is inhibited in a similar manner [15].

Associations of Ccl4 with chemical compounds

• Prostaglandin E2 inhibits production of the inflammatory chemokines CCL3 and CCL4 in dendritic cells [16].
• Mast cells accumulating in the nodes during DNFB sensitization were the predominant source of MIP-1 beta, whereas MIP-1 alpha was expressed by multiple cell types [17].
• Macrophage inflammatory protein 1 (MIP 1), initially purified from the conditioned medium of endotoxin-stimulated macrophages, is a low m.w. heparin-binding protein doublet comprising two peptides, MIP 1 alpha and MIP 1 beta [18].
• RANTES secretion from osteoblast is inhibited by differentiation promoting hormones, e.g. 1,25 (OH)2D3 and dexamethasone, whereas macrophage inflammatory protein-1 alpha (but not macrophage inflammatory protein-1 beta) and elevated calcium induce it [19].
• Functional studies of the MIP-1 beta proximal promoter indicate that it is cell-specific, and serum- and LPS-responsive in macrophages [20].

Physical interactions of Ccl4

• An ATF/CREB-binding site is essential for cell-specific and inducible transcription of the murine MIP-1 beta cytokine gene [20].
• Importantly, purified D6 retains full functional activity, shown by displaceable binding of 125I-labelled MIP-1beta (macrophage inflammatory protein-1beta) and by complete binding of the receptor to a MIP-1alpha affinity column [21].

Regulatory relationships of Ccl4

• In fact, as little as eightfold excess MIP 1 beta blocked TNF-induction by MIP 1 alpha to a significant degree [18].

Other interactions of Ccl4

• Altered thymocyte migration during experimental acute Trypanosoma cruzi infection: combined role of fibronectin and the chemokines CXCL12 and CCL4 [22].
• Although GM+ mice are able to express the chemokine RANTES, they lack the ability to express other inflammatory chemokines such as lymphotactin and MIP-1beta [23].
• However, over the first few weeks of the infection, when the susceptibility of the beige mouse lung first becomes evident, MIP-1 beta and MIP-2 chemokine expression in the lungs was lower in beige mice than in wild-type animals [14].
• We report here the resolution of MIP-1 into component peptides by SDS-hydroxylapatite chromatography, and compare the NH2-terminal sequences of the two peptides, now referred to as MIP-1 alpha and MIP-1 beta [8].
• Furthermore, these spleen cells produce cytokines including interleukin(IL)-2, IL-3, interferon-gamma, granulocyte/macrophage colony-stimulating factor, macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta, which may play an important role in the attraction of mononuclear cells to an antigen-challenging site [24].

Analytical, diagnostic and therapeutic context of Ccl4

• When mice were treated by intraperitoneal injection of HVJ cationic liposomes containing the MIP-1beta gene, the survival periods of the MIP-1beta-treated mice were significantly longer than those of control mice [2].
• To evoke antitumor immunity more efficiently, macrophage inflammatory protein-1beta (MIP-1beta) was used for gene therapy of colon cancer in mice [2].
• As the major role of the immune system is immunosurveillance against cancer, we decided to follow the morphological and functional changes of the immune system during acute and subchronic exposures to CCL4 in mice [25].
• The balance between the up-regulation of G-CSF-R and CCL4 genes, and the down-regulation of the OPN gene shown by the cDNA microarray technique might be responsible for the absence of development of an inflammatory response, lung EC activation, and lung remodelling [26].

References