Interferon (IFN)-gamma is a main mediator of keratinocyte (HaCaT) apoptosis and contributes to autocrine IFN-gamma and tumour necrosis factor-alpha production.

Konur, Abdo; Eißner, Günther; Andreesen, Reinhard; Holler, Ernst

doi:10.1111/j.1365-2133.2005.06508.x

Cited by 49 publications

(48 citation statements)

References 28 publications

(45 reference statements)

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“…Elevated relative telomerase activity was more significant when cells were treated with TNF-α and IFN-γ together. Those results were similar to previous reports about the synergic effect of TNF-α with IFN-γ in the induction of keratinocyte apoptosis 20 . Interestingly, our results about the pattern of increased telomerase activity seemed to parallel with the inhibitory effect of TNF-α and IFN-γ on cultured human keratinocyte.…”

Section: Discussionsupporting

confidence: 82%

“…In the previous report about the effect of TNF-α in epidermal keratinocyte, it showed the inhibitory effect on cell proliferation 18 . IFN-γ also showed strong inhibitory effects on cell proliferation and these effects showed synergy in present action of TNF-α [19][20][21] . Our results showed significant inhibitory effects on cell proliferation in the early passage (P0, P1) of serial cultures.…”

Section: Discussionmentioning

confidence: 99%

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The Effect of TNF-α and INF-γ on the Telomerase Activity of Cultured Human Keratinocyte

et al. 2007

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Psoriasis is a chronic inflammatory skin disease characterized by hyperproliferation and abnormal differentiation of the lesional epidermis. In pathogenesis, inflammatory cytokines such as TNF-α and IFN-γ from infiltrated T-cells seem to act a central role. Although many chronic inflammatory conditions can lead to cancer development, there is no evidence of increased incidence of cancer in psoriatic skin lesion.Telomerase is an enzyme-reverse transcriptase that protects chromosomes from degradation by stabilizing telomere length. Recent studies suggest that telomerase activity may be responsible for some part of nonmalignant proliferatory skin disease. In addition, there is evidence that telomerase activity is related with proliferation and differentiation of keratinocyte.In this experiment, we tried to evaluate the effect of TNF-α and IFN-γ to the telomerase activity and its differential effect thought the passage. The results showed increased telomerase activity according to stimulation and this extent was different from the various passage. These results suggest that the key cytokines of psoriasis, namely, TNF-α and IFN-γ increase telomerase activity at proliferative cells, which could contribute to hyperproliferation and abnormal differentiation of lesional keratinocyte. Moreover, this increased telomerase activity could partially explain the cancer incidence of psoriasis that is not increased compared to the normal population.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

The Effect of TNF-α and INF-γ on the Telomerase Activity of Cultured Human Keratinocyte

et al. 2007

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“…HaCaT cells have been proposed to be more susceptible to TRAIL-induced apoptosis 22 compared with human epidermal keratinocytes (HEKs). A role for interferon (IFN)-␥ in TRAIL-induced apoptosis 23 of primary keratinocytes has recently been reported.…”

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confidence: 99%

FasL and TRAIL Induce Epidermal Apoptosis and Skin Ulceration Upon Exposure to Leishmania major

Eidsmo

Fluur

Réthi

et al. 2007

The American Journal of Pathology

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Receptor-mediated apoptosis is proposed as an important regulator of keratinocyte homeostasis in human epidermis. We have previously reported that Fas/FasL interactions in epidermis are altered during cutaneous leishmaniasis (CL) and that keratinocyte death through apoptosis may play a pathogenic role for skin ulceration. To further investigate the alterations of apoptosis during CL, a keratinocyte cell line (HaCaT) and primary human epidermal keratinocytes were incubated with supernatants from Leishmania major-infected peripheral blood mononuclear cells. An apoptosis-specific microarray was used to assess mRNA expression in HaCaT cells exposed to supernatants derived from L. major-infected cultures. Fas and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mRNA and protein expression were significantly up-regulated, and apoptosis was detected in both HaCaT and human epidermal keratinocyte cells. The keratinocyte apoptosis was partly inhibited through blocking of Fas or FasL and even more efficiently through TRAIL neutralization. Up-regulation of Fas on keratinocytes in epidermis and the presence of FasL-expressing macrophages and T cells in dermis were previously reported by us. In this study, keratinocytes expressing TRAIL, as well as the proapoptotic receptor TRAIL-R2, were detected in skin biopsies from CL cases. We propose that activation of Fas and TRAIL apoptosis pathways, in the presence of inflammatory mediators at the site of infection, leads to tissue destruction and ulceration during CL. (Am J

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“…It has been suggested that several pathways are implicated in the widespread apoptosis of keratinocytes in SJS/TEN (24)(25)(26)(27). Involvement of cytotoxic T cells and the molecular cytotoxicity of Fas and cytotoxic enzymes, including granzyme B, perforin, and granulysin have been shown in SJS/TEN (25,27).…”

Section: Discussionmentioning

confidence: 99%

Severe Obliterative Bronchitis Associated with Stevens-Johnson Syndrome

et al. 2011

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We report a case of Stevens-Johnson syndrome (SJS) in which the patient had been diagnosed with severe obliterative bronchitis. A 29-year-old woman was admitted with a high fever and a widespread vesicular rash. She was diagnosed with SJS and betamethasone administration was started. After one month, her vesicular skin rash improved; however, she developed respiratory failure and was assisted with mechanical ventilation.Computed tomography of the chest demonstrated a hyperlucent lung with narrowing of the peripheral vessels. Bronchoscopy revealed an occlusion of the bronchus when the patient exhaled. The flow-volume curve revealed a severe obstructive pattern. The patient was diagnosed with obliterative bronchitis following SJS. She was treated with a bronchodilator and steroids, but could not breathe adequately without the ventilator. During the following year, her PaCO2 increased to 100 torr and her heart function also continued to worsen. Despite intensive treatment, she died one year and seven months after the onset of SJS. In SJS and toxic epidermal necrolysis (TEN) patients, chronic pulmonary complications are rare, but there is no effective therapy for obliterative bronchitis following SJS/TEN. Therefore, early awareness of this condition is needed and lung transplantation must be considered at an early stage of this disease.

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Interferon (IFN)-gamma is a main mediator of keratinocyte (HaCaT) apoptosis and contributes to autocrine IFN-gamma and tumour necrosis factor-alpha production.

Abstract: Taken together, our data suggest a central role for IFN-gamma in HaCaT keratinocyte apoptosis but also show the importance of co-acting mediators such as TNF-alpha, TRAIL and FasL, which potentiate the effect of paracrine and autocrine IFN-gamma and TNF-alpha release.

Cited by 49 publications

References 28 publications

The Effect of TNF-α and INF-γ on the Telomerase Activity of Cultured Human Keratinocyte

The Effect of TNF-α and INF-γ on the Telomerase Activity of Cultured Human Keratinocyte

FasL and TRAIL Induce Epidermal Apoptosis and Skin Ulceration Upon Exposure to Leishmania major

Severe Obliterative Bronchitis Associated with Stevens-Johnson Syndrome

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