CXCL17, an orphan chemokine, acts as a novel angiogenic and anti-inflammatory factor

Abstract

Lee WY, Wang CJ, Lin TY, Hsiao CL, Luo CW. CXCL17, an orphan chemokine, acts as a novel angiogenic and anti-inflammatory factor. Am J Physiol Endocrinol Metab 304: E32-E40, 2013. First published October 31, 2012; doi:10.1152/ajpendo.00083.2012.-Chemokines play pivotal roles in the recruitment of various immune cells to diverse tissues in both physiological and pathological conditions. CXCL17 is an orphan chemokine preliminarily found to be involved in tumor angiogenesis. However, its protein nature, as well as its endogenous bioactivity, has not been well clarified. Using real-time PCR, immunohistochemical staining, and Western blotting, we found that CXCL17 is highly expressed in both a constitutive and inducible manner in the rat gastric mucosa, where it undergoes endoproteolysis during protein maturation. The mature CXCL17 exhibited strong chemoattractant abilities targeting monocytes and macrophages, potentially through ERK1/2 and p38 but not JNK signaling. CXCL17 also induced the production of proangiogenic factors such as vascular endothelial growth factor A from treated monocytes. Furthermore, in contrast to other CXC chemokines that accelerate inflammatory responses, CXCL17 showed novel anti-inflammatory effects on LPS-activated macrophages. Therefore, our data suggest that CXCL17 in the gastric lamina propria may play an important role in tissue repair and anti-inflammation, both of which help to maintain the integrity of the gastric mucosa. endoproteolysis; macrophages; stomach CHEMOKINES ARE A GROUP OF CHEMOTACTIC CYTOKINES that govern the recruitment of various leukocytes to inflammation sites. In addition to promoting the trafficking of leukocytes, recent studies indicate that chemokines also play important roles in many aspects, including tumor growth, angiogenesis, organ sclerosis, and autoimmunity (21). Based on sequence homology and the numbers of amino acids between the first two cysteines, chemokines can be subdivided into C, CC, CXC, and CX 3 C subgroups (15). Chemokines bind to G protein-coupled receptors (GPCRs) on different target cells to initiate intracellular signaling cascades. Although the physiological roles and cognate receptors of most chemokines have been well characterized (34), the endogenous function as well as the receptor nature of CXCL17, the most recent chemokine ligand to be reported (17), are still unclear.CXCL17 was originally identified in 2006 by threading methods as having a protein structure similar to the CXC chemokine family (17). Although its physiological functions have not been clearly explored, two studies have proposed that CXCL17 might act as a chemokine that accelerates tumor progression (13,30). Overexpression of CXCL17 in NIH3T3 or hepatocellular carcinoma cells significantly promotes their tumor formation capability in nude mice. Microarray analyses have indicated that the CXCL17 transcript is elevated dramatically in breast and colon tumors, where its level is tightly coregulated in concert with vascular endothelial growth factor (VEGF) expression. Becau...

CXCL17 Attenuates Imiquimod-Induced Psoriasis-like Skin Inflammation by Recruiting Myeloid-Derived Suppressor Cells and Regulatory T Cells

“…Moreover, injection of anti-CCL3 Ab did not decrease IL-10 and Foxp3. Therefore, CCL5 and CCL4, but not CCL3, Our study clearly showed the immune suppressive roles of CXCL17, MDSCs, and Tregs in the setting of skin inflammatory diseases, which have been reported in cancer tissues (1,7,10,(39)(40)(41)(42)(43)(44)(45). Only limited numbers of previous reports discussed suppressive function of MDSCs in inflammatory disorders such as alopecia areata and arthritis (46)(47)(48).…”

“…Alternatively, CXCL17 is associated with antitumor immune response during early stages of pancreatic carcinogenesis through triggering the accumulation of dendritic cells at the tumor sites (9). In previous studies, other functions of CXCL17 have been reported: CXCL17 suppresses proinflammatory cytokine production from murine macrophages and acts as an anti-inflammatory factor (10). CXCL17 was also reported to be important as an antimicrobial mucosal chemokine in the pathogenesis of interstitial lung disease (3).…”

Proinflammatory effect of AbetaPP induced ST6GAL1 secretion from C2C12 myogenic cell line

“…Therefore, J774 cells were also treated with LPS to serve as a positive control in our experiments. In addition, LPS-mediated dramatic increase in the expression of inflammatory mediators have also been observed in some published studies even at low concentrations of LPS (30 ng/mL) [24]. Although the proinflammatory cytokine response to LPS alone was greater than AbetaPP751-pCMVSport6, STtyrpSVL and SP(sol)STtyr-PSVL, the response of J774 cells to soluble ST6GAL1 were statistically significant when compared with their counterparts transfected with empty vector.…”

THE CLINICAL AND PATHOGENETIC SIGNIFICANCE OF 70- AND 27-kDa HEAT SHOCK PROTEINS IN OSTEOARTHRITIS

“…Известен также как VEGF (фактор ро-ста эндотелия сосудов) корегулируемый хемокин 1 и хе-мокиноподобный белок привлечения дендритных кле-ток и моноцитов (DMC -dendritic cell-and monocyteattracting chemokine-like protein) [12]. Данный хемокин участвует в привлечении и регуляции дендритных кле-ток, моноцитов в ряде тканей.…”

“…Снижение концентрации данного хемокина прямо ассоциировано с уровнями БТШ70 и ФНОα. Де-ло в том, что экспрессия CXСL17 активируется в клет-ках под воздействием ИЛ1β и ФНОα и совместно регу-лируется с VEGF [12,15], что объясняет выявленные нами тенденции.…”