Disease relevance of CCL28

• Subsequently, we demonstrated that human and mouse CCL28 had a potent antimicrobial activity against Candida albicans, Gram-negative bacteria, and Gram-positive bacteria [1].
• Expression of CCL28 by Reed-Sternberg cells defines a major subtype of classical Hodgkin's disease with frequent infiltration of eosinophils and/or plasma cells [2].
• To date, there is little known about the presence of CCL28 in colorectal cancer [3].
• Further, the plasma CCL28 levels from patients with colon and rectal cancer were also examined [3].
• Increased serum CCL28 levels in patients with atopic dermatitis, psoriasis vulgaris and bullous pemphigoid [4].

High impact information on CCL28

• Epithelial cells in diverse gastrointestinal and nonintestinal mucosal tissues express the chemokine MEC/CCL28 [5].
• Here we demonstrate that CCR10, a receptor for MEC, is selectively expressed by IgA Ab-secreting cells (large s/cIgA(+)CD38(hi)CD19(int/-)CD20(-)), including circulating IgA(+) plasmablasts and almost all IgA(+) plasma cells in the salivary gland, small intestine, large intestine, appendix, and tonsils [5].
• A series of nontransformed mammary epithelial cell (MEC) lines were used to correlate p53 function with activation of PCD [6].
• Selective inhibition of endogenous MDGI expression in MEC by antisense phosphorothioate oligonucleotides suppresses appearance of alveolar end buds and lowers the beta-casein level in organ cultures [7].
• Moreover, application of the medium conditioned by differentiating normal MEC can reverse the phenotypes of differentiation-defective breast cancer cells bearing reduced BRCA1 functions [8].

Chemical compound and disease context of CCL28

• Thirty-two patients with refractory acute myeloid leukemia (AML) received salvage therapy with a single course of mitoxantrone 6 mg/m2 intravenous (IV) bolus, etoposide 80 mg/m2 IV for a period of 1 hour, and cytarabine (Ara-C) 1 g/m2 IV for a period of 6 hours daily for 6 days (MEC) [9].
• A phase I, dose-finding study was initiated to define a safe and effective regimen of mitoxantrone, etoposide, and cytarabine (MEC) when administered with PSC 833 to patients with early relapsed or refractory acute myeloid leukemia (AML) [10].
• Mitoxantrone, etoposide and intermediate-dose Ara-C (MEC): an effective regimen for poor risk acute myeloid leukemia [11].
• There was a decay time of 16.1 (7.1) h after the systems were removed for the blood fentanyl concentration to decrease to less than the mean MEC for the control of postoperative pain [12].
• In ductal and lobular in situ carcinomas, SA226P reacted strongly and diffusely with the remaining MEC, the CE, and the transformed luminal cells [13].

Biological context of CCL28

• We also identified the mouse homologues of CCL28 and of CCR10, which map to mouse chromosomes 13 and 11, respectively [14].
• Finally, both CCL25 and CCL28 were capable of enhancing alpha4 integrin-dependent adhesion of IgA ASCs to mucosal addressin cell adhesion molecule-1 and VCAM-1 [15].
• CCL28 has dual roles in mucosal immunity as a chemokine with broad-spectrum antimicrobial activity [1].
• In addition, CCL28 mRNA expression and protein secretion by those cells were significantly increased by the short-chain fatty acid n-butyrate, and IL-1- or flagellin-stimulated upregulation of CCL28 by colon epithelial cells was synergistically increased by pretreatment of cells with n-butyrate [16].
• CCL28 production in HaCaT cells was mediated by different signal pathways from CCL27 [17].

Anatomical context of CCL28

• CCL28 is expressed in a variety of human and mouse tissues, and it appears to be predominantly produced by epithelial cells [14].
• RT-PCR analysis demonstrated that salivary glands expressed CCL28 mRNA at the highest levels among various mouse tissues [1].
• Furthermore, the venular endothelial cells in small intestine were positive for CCL25 and CCL28, whereas those in colon were positive for CCL28, suggesting their direct roles in extravasation of IgA ASCs [15].
• In vitro, recombinant human CCL28 displays chemotactic activity for resting CD4 or CD8 T cells [14].
• In human and mouse, chemokines CCL25 and CCL28 play an important role in attracting immune cells to the gastrointestinal tract and in controlling segmental specialization of the intestinal immune system [18].

Associations of CCL28 with chemical compounds

• We report herein on the regulation of CCL28 in human colon epithelium by the proinflammatory cytokine IL-1, bacterial flagellin, and n-butyrate, a product of microbial metabolism [16].
• Taken together, these data support a role for CCL28 in contributing to allergen driven airway pathologies, show that proinflammatory cytokines can induce this signal and suggest a role for CCR10 expressing cells in airway inflammation [19].
• Myocardial norepinephrine (MNEC), epinephrine (MEC), and dopamine (MDC) concentrations in endomyocardial biopsy samples were measured using the catechol-O- methyl transferase radioenzymatic method [20].
• PATIENTS AND METHODS: A phase III randomized study was performed using valspodar plus mitoxantrone, etoposide, and cytarabine (PSC-MEC; n=66) versus MEC (n=63) to treat patients with relapsed or refractory AML and high-risk MDS [21].
• Chemotherapy consisted of cyclophosphamide 500 mg/m2 intravenously (IV) day 1, epirubicin 50 mg/m2 IV day 1, and cisplatin 80 mg/m2 IV day 1 (CE'P regimen) alternating every 4 weeks with methotrexate 30 mg/m2 IV day 1, etoposide 200 mg/m2 IV day 1, and lomustine (CCNU) 70 mg/m2 orally day 1 (MEC' regimen) until progression [22].

Regulatory relationships of CCL28

• We propose that CXCR3 promotes the recruitment of Tregs to inflamed tissues and CCR10 allows them to respond to CCL28 secreted by epithelial cells resulting in the accumulation of CCR10+ Tregs at mucosal surfaces [23].
• By contrast, CCL28 production was downregulated by inhibitors of extracellular signal-regulated kinase and NF-kappaB [17].
• Exposure of CCR10+ Tregs to CCL28 in vitro stimulated migration and adhesion to mucosal addressin cell adhesion molecule-1 and VCAM-1 [23].
• IL-1beta and TNF-alpha induce increased expression of CCL28 by airway epithelial cells via an NFkappaB-dependent pathway [24].

Other interactions of CCL28

• In contrast to CTACK, however, MEC also supports migration through CCR3 [25].
• CCR10 is known to be selectively expressed by plasma cells, whereas CCL28 attracts eosinophils via CCR3 and plasma cells via CCR10 and CCR3 [2].
• ELISA indicated that renal protein levels of TNF-alpha, but not IL-6, interferon-gamma, and CCL28, were significantly higher in the HS than the LS group (2.3 +/- 0.8 vs. 0.7 +/- 0.2 pg/mg; P = 0.036) [26].
• Peripheral blood DNA was examined for polymorphisms in genes controlling CCK: four related to CCK-1, one to the CCK gene promoter, and one related to CCK-2 [27].
• It is well known that the amidated C-terminal part of gastrin is crucial for its interaction with the classical seven transmembrane domain receptors CCK-1 or CCK-2 [28].

Analytical, diagnostic and therapeutic context of CCL28

• By immunohistochemistry, acinar epithelial cells in human and mouse salivary glands were strongly positive for CCL28 [1].
• MEC is constitutively expressed by epithelial cells; MEC mRNA is detected in cultured bronchial and mammary gland epithelial cell lines and in epithelia isolated from salivary gland and colon using laser capture microdissection, but not in the endothelial, hemolymphoid, or fibroblastic cell lines tested [25].
• In situ hybridization confirmed the expression of CCL28 mRNA in H-RS cells [2].
• Analyses by ELISA showed that the CCL28 protein level in colon tumours was significantly (P<0.001) lower than in normal tissue and that the difference in CCL28 protein level between rectal tumour and normal tissue was not significant [3].
• Xenografts constitutively expressed little, if any, CCL28 mRNA or protein [16].

References