Disease relevance of Ccl1

• In a Th2 cell transfer system of pulmonary inflammation, anti-CCL1 also failed to affect recruitment of Th2 cells to the lung following allergen challenge [1].
• Thus, induction of seven chemokines, including T cell activation gene 3 (TCA3), monocyte chemoattractant protein-1, and IFN-gamma-inducible protein-10 within the CNS during experimental autoimmune encephalomyelitis fails to occur early in the inflammatory process in TNF-deficient mice, despite local expression of monokines and IFN-gamma [2].
• Using a gelatin sponge model for delayed-type hypersensitivity (DTH), we show that TCA3 is a component of the expression phase of an anticryptococcal CMI response in mice [3].
• The genomic organizations of TCA3 was determined for two lambda phage clones and was found to be a single copy gene containing at least three exons dispersed over less than 4.7 kb [4].
• Although it has been hypothesized that the rescuing effect of CCL1 from apoptosis could be CCR8-mediated, here, we formally demonstrate the role of such receptor as its selective antagonist encoded by the MC148 gene of molluscum contagiosum virus MC148/vMCC-I inhibits v-MIP-1- and CCL1-induced rescue activity [5].

High impact information on Ccl1

• Identification of CCR8: a human monocyte and thymus receptor for the CC chemokine I-309 [6].
• These properties parallel those of endogenous I-309 receptors expressed in an HL-60 clone 15 cell line model [6].
• After transfection with the CY6 open reading frame, a mouse pre-B cell line exhibited calcium flux and chemotaxis in response to I-309 (EC50 = 2 nM for each), whereas 20 other chemokines were inactive [6].
• DNA sequence analysis indicates that the P500 and TCA3 proteins are encoded by alternative splicing products of one genomic gene [7].
• In mouse femoral arteries, CCR8 and TCA3 antigen colocalized with VSMCs and were up-regulated after injury [8].

Biological context of Ccl1

• Similarly, another beta-chemokine, TCA3, which is produced by encephalitogenic T lymphocytes, also induced chemotaxis of microglia and macrophages [9].
• The CCR8 ligands I-309 and its mouse homologue T cell activation gene 3 (TCA-3) are potent chemoattractants for Th2-polarized cells [10].
• TCA3 CAT constructs containing regions encompassing either the 0.042 kb or 2.0 kb sequence from the transcription start site were not able to direct CAT-protein synthesis [11].
• The TCA3 5' flanking sequence contained negative regulatory activity [11].
• Finally, panels of rodent-human somatic cell hybrids were used to map the I-309 gene to human chromosome 17 [12].

Anatomical context of Ccl1

• 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 [13].
• Neutrophils and macrophages responded to similar concentrations of TCA3 (3 x 10(-9) to 10(-8) M) [14].
• The CCR8 ligand, TCA3, is shown to be produced predominantly by resident microglia of the CNS in response to TNF [2].
• Lymph node cells responded to other chemokines but did not migrate to TCA3 [14].
• Neutralization of TCA3 in immunized mice results in reduced numbers of neutrophils and lymphocytes at DTH reaction sites [3].

Associations of Ccl1 with chemical compounds

• We have demonstrated for the first time that CCL1 is up-regulated in the lung following allergen challenge [1].
• There was a 60- to 80-fold induction with TCA3 CAT constructs extending between 1.324 kb and 0.324 kb upstream from the transcription start site after treatment with PMA/A23187 and a 30- to 40-fold induction with Fc epsilon RI cross-linking [11].
• Expression TCA3 in response to Con A is blocked by cyclosporin A treatment [4].
• Subnanomolar concentrations (100 pM) of TCA3 also caused integrin-mediated increases of adhesiveness to fibrinogen by neutrophils and macrophages [15].
• TCA3 is a proinflammatory murine glycoprotein that shares structural features with cytokines of the beta chemokine family and is a chemoattractant for neutrophils and monocytes [16].

Other interactions of Ccl1

• Using antibodies specific for CCR5 and CCR8, the chemotactic response to MIP-1beta and TCA-3, respectively, was reduced significantly [13].
• In addition, 11 members of the Scya gene family were found to be organized into two clusters at the borders of the Om region [17].
• Using CCR8(-/-) mice, evidence is provided that TCA3-CCR8 interactions contribute to rapid-onset CNS inflammation [2].
• Furthermore, TCA3 does not induce a Ca2 lux in cells transfected with cDNA for the C-C CKR-1 chemokine receptor, supporting the conclusion that there are distinct receptors for TCA3 [14].
• The TCA3 gene encodes a proinflammatory cytokine related to IL-8 and MCP-1 (JE) [18].

Analytical, diagnostic and therapeutic context of Ccl1

• Northern blot analysis showed that TCA3 message appeared in mast cells within 2 h after induction, with a t1/2 of 30 min [11].
• A sensitive and specific capture ELISA for TCA3 quantitation was developed, allowing measurement of TCA3 levels in the supernatants from activated murine splenocytes and T cell clones [18].
• Western blotting also demonstrated that all four mAb specifically recognize rTCA3, native TCA3 produced by activated mouse T cells, and the nonglycosylated TCA3 core protein [18].
• We compared by reverse transcriptase PCR the thyroidal expression of 10 chemokines (CCL1 through 5 and CXCL9 through 13) in thyr-IFNgamma transgenics and wild-type littermates [19].
• Moreover, intranasal administration of BP to mice enhanced mRNA levels of TCA3, the mouse orthologue of CCL1, in lung [20].

References