Anatomy & Biological Anthropology 2023 KCI Impact Factor : 0.33
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pISSN : 2671-5651 / eISSN : 2671-566X
- https://journal.kci.go.kr/aba
KJCKorea
Journal Central
Iron chelator induces MIP-3α/CCL20 in human intestinal epithelial cells: implication for triggering mucosal adaptive immunity
- Anatomy & Biological Anthropology
- Abbr : Anat Biol Anthropol
- 2004, 17(4), pp.297~312
- DOI : 10.11637/aba.2004.17.4.297
- Publisher : 대한체질인류학회
- Research Area : Medicine and Pharmacy > Anatomy
이명수 1, Hyun-ju Lee 1, 한원철 1, 오재민 1, 전창덕 1
1원광대학교
Candidate
ABSTRACT
A previous report by this laboratory demonstrated that bacterial iron chelator (siderophore) triggers inflammatory signals, including the production of CXC chemokine IL-8, in human intestinal epithelial cells (IECs). Microarraybased gene expression profiling revealed that iron chelator also induces CC chemokine MIP-3α/CCL20. As CCL20 is chemotactic for the cells involved in host adaptive immunity, this suggests that iron chelator may stimulate IECs to have the capacity to link mucosal innate and adaptive immunity. The basal medium from iron chelator deferoxamine (DFO)-treated HT-29 monolayers was as chemotactic as rhCCL20 at equivalent concentrations to attract CCR6± cells. The increase of CCL20 protein secretion appeared to correspond to that of CCL20 mRNA levels, as determined by real-time quantitative RT-PCR. The efficacy of DFO at inducing CCL20 mRNA was also observed in human Peripheral Blood Mononuclear Cells (PBMCs) and in THP-1 cells, but not in Human Umbillical Vein Endothelial Cells (HUVECs). Interestingly, unlike other proinflammatory cytokines, such as TNF-α and IL-1β, a time-dependent experiment revealed that DFO slowly induces CCL20, suggesting a novel mechanism of action. A pharmacologic study also revealed that multiple signaling pathways are differentially involved in CCL20 production by DFO, while some of those pathways are not involved in TNF-α-induced CCL20 production. Collectively, these results demonstrate that, in addition to some bacterial products known to induce host adaptive immune responses, direct chelation of host iron by infected bacteria may also contribute to the initiation of host adaptive immunity in the intestinal mucosa.
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