Leukotrienes B4, C4 and D4 stimulate DNA synthesis in cultured human epidermal keratinocytes

Kragballe, Knud; Desjarlais, L.; Voorhees, John J.

doi:10.1111/j.1365-2133.1985.tb02043.x

Cited by 162 publications

(64 citation statements)

References 26 publications

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“…Although there is no published study on the effects of LTB 4 on human tendon fibroblasts, our results agree with previous reports obtained using other cell/tissue types. For example, LTB 4 was shown to stimulate DNA synthesis in cultured human epidermal keratinocytes at picomolar concentrations (Kragballe et al, 1985). Also, in arterial smooth muscle cells, LTB 4 at 10 pM was shown to stimulate cell proliferation and DNA synthesis (Palmberg et al, 1987(Palmberg et al, , 1989.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, we have shown that exogenous addition of PGE 2 at a dose of 100 ng/ml decreases proliferation and collagen production in human patellar tendon fibroblasts (HPTFs) (Cilli et al, 2004). On the other hand, LTB 4 at picomolar concentrations has been shown to stimulate DNA synthesis in cultured human epidermal keratinocytes and to induce proliferation of arterial smooth muscle cells in primary culture (Kragballe et al, 1985;Palmberg et al, 1989). Also, leukotrienes at low concentrations (0.1 to 1 nM) stimulate collagen synthesis of lung fibroblasts (Phan et al, 1987(Phan et al, , 1988.…”

Section: Introductionmentioning

confidence: 99%

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Leukotriene B4 at low dosage negates the catabolic effect of prostaglandin E2 in human patellar tendon fibroblasts

Thampatty¹,

Im²,

Wang³

2006

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Tendinopathy often involves inflammation and matrix degeneration. The inflammatory mediators such as prostaglandin E 2 (PGE 2 ) and leukotriene B 4 (LTB 4 ) are implicated in the development of tendinopathy. Therefore, the purpose of this study was to determine the effect of PGE 2 and LTB 4 on the proliferation of human patellar tendon fibroblasts (HPTFs), the gene expression of collagen type I, MMP-1 and MMP-3, as well as the protein secretion of these gene products by the cells. The results showed that LTB 4 at low doses (0.1 and 1 nM) significantly increased cell proliferation compared to controls and LTB 4 at 0.1 nM negated the PGE 2 -induced decrease in cell proliferation. In addition, PGE 2 at 100 ng/ml significantly increased the expression of MMP-1 and MMP-3 at both mRNA and protein levels. These stimulatory effects were significantly diminished by co-treatment with LTB 4 at 0.1 nM. Finally, neither PGE 2 nor LTB 4 treatment affected collagen type I gene expression. These results suggest that low levels of LTB 4 counterbalance the negative effects mediated by PGE 2 on tendon fibroblast proliferation and MMP production, which may lead to matrix degradation. Thus, our findings suggest that although LTB 4 is generally thought to be pathogenic, low levels of LTB 4 are actually beneficial in maintaining tendon tissue homeostasis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Leukotriene B4 at low dosage negates the catabolic effect of prostaglandin E2 in human patellar tendon fibroblasts

Thampatty¹,

Im²,

Wang³

2006

Gene

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“…The maximum effect of the leukotrienes was about half of that obtained with PDGF, and at suboptimal concentrations of PDGF, an additive effect of the leukotrienes was obtained. 341 Growth-promoting effects of leukotrienes have also been observed in cultures of glomerular epithelial cells, 3 4 2 3 4 3 epidermal keratinocytes, 344 fibroblasts, 345 and endothelial cells. 346 In recent experiments, we have continued to examine the growth-stimulatory effect of LTB 4 on rat aortic smooth muscle cells, with particular emphasis on the role of endogenous cyclooxygenase products (unpublished observations).…”

Section: Role Of Prostaglandins and Leukotrienesmentioning

confidence: 94%

Regulation of differentiated properties and proliferation of arterial smooth muscle cells.

et al. 1990

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“…A critical role of neutrophils in driving the hyperproliferation in the flaky skin mouse mutant has been demonstrated, and it is possible that neutrophils will prove to play a similar role in K5-I B␣ mice (22). It is known that neutrophils produce reactive oxygen species, lipid mediators, and proteolytic enzymes that potentially can affect keratinocyte proliferation (23)(24)(25). Of interest is also the infiltration of B220(ϩ) Pax5(Ϫ) cells with dendritic morphology, which we identify as plasmacytoid dendritic cells.…”

Section: Discussionmentioning

confidence: 99%

Tumor necrosis factor receptor 1-mediated signaling is required for skin cancer development induced by NF-κB inhibition

Lind

Rozell²,

Wallin³

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

106

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T he Rel͞NF-B transcription factors have a central role in several cellular processes, including proliferation, cell adhesion, apoptosis, and regulation of the immune response (1). Under nonstimulating conditions, NF-B is retained in the cytoplasm in an inactive form because of its interaction with the inhibitory proteins I Bs. In response to an activating stimulus, I B is phosphorylated by an I B kinase (IKK) complex, which targets it for degradation by the proteasome, releasing NF-B, which translocates to the nucleus, where it regulates the transcription of target genes.Evidence gathered from studies during recent years have shown that NF-B has a growth inhibitory function in the skin. Initial studies showed that overexpression of the NF-B subunits p50 or p65 in the basal layer of the murine epidermis by using a keratin 14 (K14) promoter leads to hypoplasia of the epidermis, whereas expression of a superrepressor form of the inhibitor of NF-B type ␣ (I B␣) results in hyperplasia (2). Although K14-I B␣ mice die shortly after birth (day 7), we have shown that mice with keratin 5 (K5)-directed expression of I B␣ (K5-I B␣) to the basal layer of the epidermis survive to adulthood (3). Not only do these mice develop hyperplasia of the epidermis, but the skin phenotype of K5-I B␣ mice is also characterized by an intense neutrophil-dominated inflammation of the skin and an early development of squamous cell carcinomas (SCC).Recent data suggest that human sporadic SCC may show a block in NF-B signaling based on nuclear exclusion of the RelA NF-B subunit (ref. 4 and M.v.H., unpublished results). Furthermore, it was recently shown that coexpression of a superrepressor form of I B␣ and Ha-Ras results in neoplasia resembling invasive SCC in human keratinocytes transplanted to severe combined immunodeficient (scid͞scid) mice, supporting the relevance of a NF-B block in the induction of human SCC (4).Inflammation of the skin with neutrophil infiltration and hyperproliferation is also seen in female heterozygous Ikk␥-deficient mice, which develop a condition similar to the human X-linked disorder Incontinentia Pigmenti (IP) (5, 6). IKK␥ is the regulatory subunit of the IKK complex, which, in addition, contains the two catalytic subunits IKK␣ (IKK1) and IKK␤ (IKK2) (1). It is now well established that human IP results from loss-of-function mutations in the IKK␥ gene (7). Interestingly, subungual keratoacanthoma-like tumors and cases of SCC have been reported as late manifestations of IP (8-11).The catalytic IKK␤ subunit is necessary for activation of NF-B in response to proinflammatory stimuli (1). Skin-specific deletion of the IKK␤ gene, K14-Cre͞Ikk2 FL/FL , was recently shown to result in an inflammatory phenotype with concomitant hyperproliferation of the epidermis (12), very similar to what is seen in the K5-I B␣ mice. Because the K14-Cre͞Ikk2 FL/FL mice die between day 7 and day 9 after birth, it is currently not known whether they, similar to K5-I B␣ mice, are prone to develop SCC.Besides inf lammation and hyperprolifera...

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Leukotrienes B4, C4 and D4 stimulate DNA synthesis in cultured human epidermal keratinocytes

Cited by 162 publications

References 26 publications

Leukotriene B4 at low dosage negates the catabolic effect of prostaglandin E2 in human patellar tendon fibroblasts

Leukotriene B4 at low dosage negates the catabolic effect of prostaglandin E2 in human patellar tendon fibroblasts

Regulation of differentiated properties and proliferation of arterial smooth muscle cells.

Tumor necrosis factor receptor 1-mediated signaling is required for skin cancer development induced by NF-κB inhibition

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