RETRACTED: IL-12 Deficiency Exacerbates Inflammatory Responses in UV-Irradiated Skin and Skin Tumors

Meeran, Syed Musthapa; Thejass, P.; Katiyar, Säntosh K.

doi:10.1038/jid.2008.140

Cited by 72 publications

(57 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Using wild-type (C3H/HeN) and IL-12-knockout mice Meeran et al demonstrated that IL-12-deficiency significantly enhanced levels of pro-inflammatory cytokines (IL-1 β, TNF-α and IL-6) and COX-2 as well as leukocyte infiltration (MPO activity) following UV treatment (80% UVB; 180 mJ/cm 2 ) (ref. 32 ). As shown in Table 1, under our conditions UVB treatment had no significant effect on IL-12(p40) plasma expression.…”

Section: Discussionmentioning

confidence: 99%

Differential modulation of inflammatory markers in plasma and skin after single exposures to UVA or UVB radiation in vivo

Vostalová¹,

Svobodová²,

Galandáková³

et al. 2013

BIOMED PAP

View full text Add to dashboard Cite

Background. Solar light generates inflammatory responses in exposed skin. These effects are generally attributed to UVB light. However, skin is exposed to a huge quantum of UVA photons as UVA is a predominant part of sunlight and the radiation used in tanning beds. We examined the effects of a single exposure to UVA and UVB wavebands on cytokine levels in skin and plasma, myeloperoxidase (MPO) activity, expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) in skin. Methods. Hairless mice were irradiated with either UVA (10 or 20 J/cm 2 ) or UVB (200 or 800 mJ/cm 2 ). The effects were assessed after 4/24 h. Plasma cytokine levels were evaluated using a Bio-Plex cytokine assay. Cytokine, iNOS and COX-2 levels in skin were determined by Western blot. Skin MPO activity was monitored spectrophotometrically. Results. UVB induced up-regulation of interleukin-1β (IL-1β) and interleukin-6 (IL-6) and decrease in interleukin-10 (IL-10) mainly after 4 h. In contrast, UVA caused increase in levels of tumor necrosis factor-alpha (TNF-α) and IL-6 after 4 h and up-regulated IL-10 and interleukin-12 (IL-12) after 24 h. The increase in MPO activity from infiltrated leucocytes was observed only in UVB irradiated animals. iNOS was up-regulated 4 h after UVA and UVB treatment. No significant effect on COX-2 expression was detected. Conclusions. UVA and UVB light affected several inflammatory markers. For individual waveband, changes in plasma parameters did not correlate with those in skin. Thus evaluation of plasma samples cannot simply be replaced by determination in skin specimens and vice versa.

show abstract

Section: Discussionmentioning

confidence: 99%

Differential modulation of inflammatory markers in plasma and skin after single exposures to UVA or UVB radiation in vivo

Vostalová¹,

Svobodová²,

Galandáková³

et al. 2013

BIOMED PAP

View full text Add to dashboard Cite

show abstract

“…Enhanced expression of COX-2 in skin exposed to UV radiation has been identified as a risk factor for the development of skin cancer. (5,6) Cyclooxygenase-2 generates prostaglandins that are thought to play a central role in orchestrating the events involved in cancer invasion and metastasis. Prostaglandin E 2 (PGE 2 ) exerts its effects through G-protein coupled receptors (EP1, EP2, EP3, and EP4) and has been implicated in angiogenesis, invasion, and metastasis.…”

mentioning

confidence: 99%

Timosaponin AIII inhibits melanoma cell migration by suppressing COX‐2 and in vivo tumor metastasis

Kim

et al. 2016

Cancer Science

View full text Add to dashboard Cite

Melanoma is the leading cause of death from skin disease, due in large part to its propensity to metastasize. We examined the effects of timosaponin AIII, a compound isolated from Anemarrhena asphodeloides Bunge, on melanoma cancer cell migration and the molecular mechanisms underlying these effects using B16-F10 and WM-115 melanoma cells lines. Overexpression of COX-2, its metabolite prostaglandin E 2 (PGE 2 ), and PGE 2 receptors (EP2 and EP4) promoted cell migration in vitro. Exposure to timosaponin AIII resulted in concentration-dependent inhibition of cell migration, which was associated with reduced levels of COX-2, PGE 2 , and PGE 2 receptors. Transient transfection of COX-2 siRNA also inhibited cell migration. Exposure to 12-O-tetradecanoylphorbal-13-acetate enhanced cell migration, whereas timosaponin AIII inhibited 12-O-tetradecanoylphorbal-13-acetate-induced cell migration and reduced basal levels of EP2 and EP4. Moreover, timosaponin AIII inhibited activation of nuclear factor-kappa B (NF-jB), an upstream regulator of COX-2 in B16-F10 cells. Consistent with our in vitro findings, in vivo studies showed that timosaponin AIII treatment significantly reduced the total number of metastatic nodules in the mouse lung and improved histological alterations in B16-F10-injected C57BL ⁄ 6 mice. In addition, C57BL ⁄ 6 mice treated with timosaponin AIII showed reduced expression of COX-2 and NF-jB in the lung. Together, these results indicate that timosaponin AIII has the capacity to inhibit melanoma cell migration, an essential step in the process of metastasis, by inhibiting expression of COX-2, NF-jB, PGE 2, and PGE 2 receptors. M elanoma is the most deadly type of skin cancer, accounting for approximately 80% of deaths caused by skin cancer.(1) Melanoma is particularly deadly due to its propensity to metastasize; clinical trials indicate that melanoma shows preferential metastasis to the lung, brain, liver, and skin. Moreover, melanoma is highly resistant to conventional chemotherapeutics.(2) Given the rising incidence of melanoma and the lack of effective therapies, development of new chemicals targeting the complex genetic networks involved in melanoma metastasis should provide new treatment strategies for this devastating disease. (3,4) Two COX isoforms with distinct physiologic functions have been identified: COX-1 and COX-2. COX-1 is expressed constitutively in many tissues and has an important role in the maintenance of homeostasis. In contrast, COX-2 is an inducible enzyme that is activated by extracellular stimuli, such as UV radiation. Enhanced expression of COX-2 in skin exposed to UV radiation has been identified as a risk factor for the development of skin cancer. (5,6) Cyclooxygenase-2 generates prostaglandins that are thought to play a central role in orchestrating the events involved in cancer invasion and metastasis. Prostaglandin E 2 (PGE 2 ) exerts its effects through G-protein coupled receptors (EP1, EP2, EP3, and EP4) and has been implicated in angiogenesis, invasion, and metastasis. (7,8)...

show abstract

“…1 UVBinduced skin inflammatory reactions constitute a potent tumor-promoting event that contributes to photocarcinogenesis. [14][15][16] Thus, development of a method for regulating UVB-induced acute effects is important for protection against photocarcinogenesis. However, the molecular mechanisms by which UVB induces acute effects on the skin have not been fully clarified.…”

mentioning

confidence: 99%

Phospholipase Cɛ has a crucial role in ultraviolet B-induced neutrophil-associated skin inflammation by regulating the expression of CXCL1/KC

Oka

Edamatsu

Kunisada

et al. 2011

Laboratory Investigation

View full text Add to dashboard Cite

Phospholipase C (PLC) e is a phosphoinositide-specific PLC regulated by small GTPases including Ras and Rap. We previously demonstrated that PLCe has an important role in the development of phorbol ester-induced skin inflammation. In this study, we investigated the role of PLCe in ultraviolet (UV) B-induced acute inflammatory reactions in the skin. Wild-type (PLCe þ / þ ) and PLCe gene knockout (PLCe À/À ) mice were irradiated with a single dose of UVB at 1, 2.5, and 10 kJ/m 2 on the dorsal area of the skin, and inflammatory reactions in the skin were histologically evaluated up to 168 h after irradiation. In PLCe þ / þ mice, irradiation with 1 and 2.5 kJ/m 2 UVB resulted in dose-dependent neutrophil infiltration in the epidermis at 24 and 48 h after irradiation. When mice were irradiated with 10 kJ/m 2 of UVB, most mice developed skin ulcers by 48 h and these ulcers became more severe at 168 h. In PLCe À/À mice, UVB (1 or 2.5 kJ/m 2 )-induced neutrophil infiltration was markedly suppressed compared with PLCe þ / þ mice. The suppression of neutrophil infiltration in PLCe À/À mice was accompanied by attenuation of UVB-induced production of CXCL1/keratinocyte-derived chemokine (KC), a potent chemokine for neutrophils, in the whole skin. Cultured epidermal keratinocytes and dermal fibroblasts produced CXCL1/KC in a PLCe-dependent manner after UVB irradiation, and the UVB-induced upregulation of CXCL1/KC in these cells was significantly abolished by a PLC inhibitor. Furthermore, UVB-induced epidermal thickening was noticeably reduced in the skin of PLCe À/À mice. These results indicate that PLCe has a crucial role in UVB-induced acute inflammatory reactions such as neutrophil infiltration and epidermal thickening by at least in part regulating the expression of CXCL1/KC in skin cells such as keratinocytes and fibroblasts.

show abstract

RETRACTED: IL-12 Deficiency Exacerbates Inflammatory Responses in UV-Irradiated Skin and Skin Tumors

Cited by 72 publications

References 34 publications

Differential modulation of inflammatory markers in plasma and skin after single exposures to UVA or UVB radiation in vivo

Differential modulation of inflammatory markers in plasma and skin after single exposures to UVA or UVB radiation in vivo

Timosaponin AIII inhibits melanoma cell migration by suppressing COX‐2 and in vivo tumor metastasis

Phospholipase Cɛ has a crucial role in ultraviolet B-induced neutrophil-associated skin inflammation by regulating the expression of CXCL1/KC

Contact Info

Product

Resources

About