Roxithromycin downregulates production of CTACK/CCL27 and MIP-3α/CCL20 from epidermal keratinocytes

Karakawa, Masaru; Komine, Mayumi; Tamaki, Kunihiko; Ohtsuki, Mamitaro

doi:10.1007/s00403-010-1068-x

Cited by 5 publications

(4 citation statements)

References 32 publications

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“…To investigate the effect of TNFα and IFNγ on CTACK/CCL27 production by keratinocytes, we stimulated normal human keratinocytes (NHEKs) with TNFα in the presence or absence of IFNγ, and evaluated the supernatant CTACK/CCL27 concentration. We set the concentration of TNFα at 30 ng/ml, which is the minimal essential concentration for the complete induction of CTACK/CCL27, as seen in our previous experiments (Karakawa et al, ). At 24 h after stimulation, TNFα induced CTACK/CCL27 production.…”

Section: Resultsmentioning

confidence: 99%

CCL27 Is Downregulated by Interferon Gamma via Epidermal Growth Factor Receptor in Normal Human Epidermal Keratinocytes

Karakawa

Komine

Hanakawa

et al. 2014

Journal Cellular Physiology

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The cutaneous T cell-attracting chemokine (CTACK)/CCL27 is indispensable in skin inflammation. CTACK/CCL27 is exclusively produced by epidermal keratinocytes to attract CCR10-expressing T lymphocytes to the skin. We investigated the mechanism of CTACK/CCL27 production from normal human epidermal keratinocytes (NHEKs) by the proinflammatory cytokines TNFα and IFNγ. CTACK/CCL27 production was induced by TNFα via ERK, JNK, p38, and NFκB. The induction of CTACK/CCL27 by TNFα was suppressed by IFNγ via a pathway dependent on JAK, STAT1, and STAT3. Our results also demonstrated that IFNγ and TNFα induced the phosphorylation of EGFR and the following phosphorylation of ERK, which is partly responsible for the suppressive effect of IFNγ on TNFα-induced production of CTACK/CCL27. Peri-lesional skin of psoriasis demonstrates early inflammatory changes as we have previously reported. CTACK/CCL27 expression was diffuse in the peri-lesional epidermis, while it was restricted to basal layer in lesional epidermis, suggesting that CTACK/CCL27 expression was induced in the early stage of psoriatic plaque formation, and IFNγ could participate in the suppression of CTACK/CCL27 expression in the lesional epidermis, reflecting the later stage of psoriatic plaque formation. Our study suggests that CTACK/CCL27 may have a pivotal role in the early stage of psoriasis plaque formation, but should be downregulated in the later stage to induce inflammation characteristic for chronic psoriasis plaques.

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Section: Resultsmentioning

confidence: 99%

CCL27 Is Downregulated by Interferon Gamma via Epidermal Growth Factor Receptor in Normal Human Epidermal Keratinocytes

Karakawa

Komine

Hanakawa

et al. 2014

Journal Cellular Physiology

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Section: Western Blot Analysis Of Mapk and Nf-jbmentioning

confidence: 99%

“…T helper-2 cells (1 9 10 6 ) were plated into six-well plates and pretreated with 20 and 40 lg/ml of roxithromycin [33], 1 h prior to a 30 min treatment with anti-CD3 (5 lg/ml) [34]. Nuclear and cytoplasmic fractions of lung were prepared as previously described [34]. Whole cell lysates were prepared in 40 mL of lysis buffer [50 mM Tris (pH 7.6), 150 mM NaCl, 5 mM EDTA (pH 8.0), 0.6 % NP-40, 1 mM Na 3 VO 4 , 20 mM b-glycerophosphate, 1 mM fluoride, 2 mM p-nitrophenyl phosphate and 1:25 Complete Mini Protease Inhibitor cocktail (Boehringer, Mannheim, Germany)].…”

Section: Western Blot Analysis Of Mapk and Nf-jbmentioning

confidence: 99%

Short-term roxithromycin treatment attenuates airway inflammation via MAPK/NF-κB activation in a mouse model of allergic asthma

Chu

Xue

et al. 2012

Inflamm. Res.

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“…NF-κB plays an important role during cellular responses to inflammatory stimuli and general responses to pathogens in a number of different cell types and is inhibited by the IκB molecule. IκB phosphorylation and its subsequent degradation releases NF-κB triggering transcription of many nuclear genes involved in pro-carcinoma processes, including chemokine CCL20 and targeting NF-κB by its specific inhibitors results in suppression of CCL20 expression in cells (21). Besides of the NF-κB-dependent CCL20 expression, it is known that the promoter region of CCL20 contains binding sites for the Ets transcription factor which is activated by ERK1/2 suggesting a role of the Ras-MAPK-pathway in CCL20 expression (22).…”

Section: Introductionmentioning

confidence: 99%

Mutations in BALB mitochondrial DNA induce CCL20 up-regulation promoting tumorigenic phenotypes

Sligh

Janda

Jandova

2014

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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mtDNA mutations are common in human cancers and are thought to contribute to the process of neoplasia. We examined the role of mtDNA mutations in skin cancer by generating fibroblast cybrids harboring a mutation in the gene encoding the mitochondrial tRNA for arginine. This somatic mutation (9821insA) was previously reported in UV-induced hyperkeratotic skin tumors in hairless mice and confers specific tumorigenic phenotypes to mutant cybrids. Microarray analysis revealed and RT-PCR along with Western blot analysis confirmed the up-regulation of CCL20 and its receptor CCR6 in mtBALB haplotype containing the mt-Tr 9821insA allele compared to wild type mtB6 haplotype. Based on reported role of CCL20 in cancer progression we examined whether the hyper-proliferation and enhanced motility of mtBALB haplotype would be associated with CCL20 levels. Treatment of both genotypes with recombinant CCL20 (rmCCL20) resulted in enhanced growth and motility of mtB6 cybrids. Furthermore, the acquired somatic alteration increased the in vivo tumor growth of mtBALB cybrids through the up-regulation of CCL20 since neutralizing antibody significantly decreased in vivo tumor growth of these cells; and tumors from anti-CCL20 treated mice injected with mtBALB cybrids showed significantly decreased CCL20 levels. When rmCCL20 or mtBALB cybrids were used as chemotactic stimuli, mtB6 cybrids showed increased motility while anti-CCL20 antibody decreased the migration and in vivo tumor growth of mtBALB cybrids. Moreover, the inhibitors of MAPK signaling and NF-κB activation inhibited CCL20 expression in mtBALB cybrids and decreased their migratory capabilities. Thus, acquired mtDNA mutations may promote tumorigenic phenotypes through up-regulation of chemokine CCL20.

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Roxithromycin downregulates production of CTACK/CCL27 and MIP-3α/CCL20 from epidermal keratinocytes

Cited by 5 publications

References 32 publications

CCL27 Is Downregulated by Interferon Gamma via Epidermal Growth Factor Receptor in Normal Human Epidermal Keratinocytes

CCL27 Is Downregulated by Interferon Gamma via Epidermal Growth Factor Receptor in Normal Human Epidermal Keratinocytes

Short-term roxithromycin treatment attenuates airway inflammation via MAPK/NF-κB activation in a mouse model of allergic asthma

Mutations in BALB mitochondrial DNA induce CCL20 up-regulation promoting tumorigenic phenotypes

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