Evidence for modulation of human epidermal differentiation and remodelling by CD40

Concha, Miguel; Vidal, María Antonia; Moreno, Inmaculada; Salem, Christian Copley; Figueroa, Carlos D.; Schmitt, Daniel; Pèguet‐Navarro, Josette

doi:10.1046/j.1365-2133.2003.05300.x

Cited by 6 publications

(10 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An extra support for a role of B2R agonists in keratinocyte differentiation is our observation of moderated (pro)filaggrin expression following stimulation of subconfluent cells with LBK, a novel effect that has not been described before in human keratinocytes. Comparative control experiments carried out to activate CD40, a molecule associated to keratinocyte differentiation (Concha et al, 2003), confirmed that the response evoked by LBK was indeed moderated.…”

Section: Figuresupporting

confidence: 57%

“…Human keratinocyte culture Cultures were prepared as previously described (Concha et al, 2003). Briefly, skin pieces split cut with a keratome device were incubated for 1 h at 371C with 0.05% trypsin (Life Technologies, Rockville, Maryland) to obtain epidermal sheets that were then pooled in Hanks' balanced salt solution (Life Technologies) supplemented with 10% fetal bovine serum (Hyclone, Logan, Utah).…”

Section: Methodsmentioning

confidence: 99%

“…Controls were carried out simultaneously by culturing cells in the absence of ligand and using B1R and B2R antagonists. Positive controls were performed with the M89 monoclonal antibody that activates CD40 to elicit keratinocyte differentiation; its specificity was assessed by replacing M89 by an unrelated mouse IgG 1 (Concha et al, 2003). Homogenates were prepared in 50 mM Tris-HCl, pH 7.4, containing 150 mM NaCl, 1 mM EDTA, 1 mM EGTA, 1 mM b-mercaptoethanol, 9 M urea, 1 mM phenylmethane-sulfonyl fluoride, 1 mM NaF, 1mM Na 3 VO 4 , 1 mg per mL aprotinin, 1 mg per mL pepstatin, and 1 mg per mL leupeptin).…”

Section: Effect Of Kinin Receptor Antagonists and Inhibitorsmentioning

confidence: 99%

See 2 more Smart Citations

Kinin B2 Receptor-Coupled Signal Transduction in Human Cultured Keratinocytes

Vidal

Astroza

Matus

et al. 2005

Journal of Investigative Dermatology

View full text Add to dashboard Cite

Kinins are key pro-inflammatory peptides that exhibit mitogenic effects in tissue-specific cellular systems. Since the life span of the keratinocyte is regulated by receptors that control proliferation and differentiation, and since both processes are affected during wound healing, we have examined the consequence of kinin B2 receptors (B2R) activation in cultured human keratinocytes. Stimulation of keratinocytes by Lys-bradykinin (LBK) induced a rapid and sustained phosphorylation of 42/44 mitogen-activated protein kinase (MAPK) that translocated to the nucleus, and decreased only after 120 min of stimulation. Kinin B1 and B2 receptor (B1R and B2R) antagonists showed that phosphorylation was mainly because of B2R activation. The GF109203X inhibitor almost completely abolished the effect of LBK, suggesting the involvement of protein kinase C in the signal cascade. MAPK phosphorylation was partially dependent on epidermal growth factor receptor transactivation as assessed by the selective inhibitor, AG1478. LBK stimulation did not result in cell proliferation, but produced a rapid c-Fos expression, nuclear translocation of nuclear factor-kappaB, and a moderated (pro)filaggrin synthesis, indicating that it may modulate cell differentiation. Our results support the view that kinins may affect the life span of human keratinocytes and highlight the importance that kinin peptides may have in the pathogenesis and/or progression of skin diseases.

show abstract

Section: Figuresupporting

confidence: 57%

Section: Methodsmentioning

confidence: 99%

Section: Effect Of Kinin Receptor Antagonists and Inhibitorsmentioning

confidence: 99%

See 1 more Smart Citation

Kinin B2 Receptor-Coupled Signal Transduction in Human Cultured Keratinocytes

Vidal

Astroza

Matus

et al. 2005

Journal of Investigative Dermatology

View full text Add to dashboard Cite

show abstract

“…A limited number of in vitro studies on CD40 ligation of human primary IFNγ-stimulated ECs showed that these cells express ICAM-1 and secrete RANTES (CCL5), TNFα, IL-6, IL-8, and MCP-1 (CCL2) (Denfeld et al , 1996; Gaspari et al , 1996; Peguet-Navarro et al , 1997; Companjen et al , 2002; Pasch et al , 2004). In addition, there is evidence that CD40-activated ECs stop proliferating and start differentiating (Peguet-Navarro et al , 1997; Grousson et al , 2000; Concha et al , 2003; Villarroel Dorrego et al , 2006). However, the full spectrum of effects mediated by CD40 ligation on the response of ECs is still unknown.…”

Section: Introductionmentioning

confidence: 99%

CD40-Mediated Amplification of Local Immunity by Epithelial Cells Is Impaired by HPV

Tummers

Goedemans

Jha

et al. 2014

Journal of Investigative Dermatology

View full text Add to dashboard Cite

The interaction between the transmembrane glycoprotein surface receptor CD40 expressed by skin epithelial cells (ECs) and its T-cell–expressed ligand CD154 was suggested to exacerbate inflammatory skin diseases. However, the full spectrum of CD40-mediated effects by ECs underlying this observation is unknown. Therefore, changes in gene expression after CD40 ligation of ECs were studied by microarrays. CD40-mediated activation for 2 hours stimulated the expression of a coordinated network of immune-involved genes strongly interconnected by IL8 and TNF, whereas after 24 hours anti-proliferative and anti-apoptotic genes were upregulated. CD40 ligation was associated with the production of chemokines and the attraction of lymphocytes and myeloid cells from peripheral blood mononuclear cells (PBMCs). Thus, CD40-mediated activation of ECs resulted in a highly coordinated response of genes required for the local development and sustainment of adaptive immune responses. The importance of this process was confirmed by a study on the effects of human papilloma virus (HPV) infection to the EC's response to CD40 ligation. HPV infection clearly attenuated the magnitude of the response to CD40 ligation and the EC's capacity to attract PBMCs. The fact that HPV attenuates CD40 signaling in ECs indicates the importance of the CD40-CD154 immune pathway in boosting cellular immunity within epithelia.

show abstract

“…CD40 expression and function has been described on a variety of cell types [4][5][6][7] , including neurons 8 . Activation of the CD40 pathway is well-known to promote proliferation, survival, differentiation and maturation in a variety of immune and other cell types [9][10][11][12][13][14][15][16][17][18][19][20] .…”

Section: Introductionmentioning

confidence: 99%

Modulation of neuronal differentiation by CD40 isoforms

Hou

Obregon

Lou

et al. 2008

Biochemical and Biophysical Research Communications

View full text Add to dashboard Cite

Neuron differentiation is a complex process involving various cell-cell interactions, and multiple signaling pathways. We showed previously that CD40 is expressed and functional on mouse and human neurons. In neurons, ligation of CD40 protects against serum withdrawal-induced injury and plays a role in survival and differentiation. CD40 deficient mice display neuron dysfunction, aberrant neuron morphologic changes, and associated gross brain abnormalities. Previous studies by Tone and colleagues suggested that 5 isoforms of CD40 exist with 2 predominant isoforms expressed in humans: signal-transducible CD40 type I and a C-terminal truncated, non-signaltransducible CD40 type II. We hypothesized that differential expression of CD40 isoform type I and type II in neurons may modulate neuron differentiation. Results show that adult wild-type, and CD40 −/− deficient mice predominantly express CD40 type I and II isoforms. Whereas adult wildtype mice express mostly CD40 type I in cerebral tissues at relatively high levels, in age and gender-matched CD40 −/− mice CD40 type I expression was almost completely absent; suggesting a predominance of the non-signal-transducible CD40 type II isoform. Younger, 1 day old wildtype mice displayed less CD40 type I, and more CD40 type II, as well as, greater expression of soluble CD40 (CD40L/CD40 signal inhibitor), compared with 1 month old mice. Neuron-like N2a cells express CD40 type I and type II isoforms while in an undifferentiated state, however once induced to differentiate, CD40 type I predominates. Further, differentiated N2a cells treated with CD40 ligand express high levels of neuron specific nuclear protein (NeuN); an effect reduced by anti-CD40 type I siRNA, but not by control (non-targeting) siRNA. Altogether these data suggest that CD40 isoforms may act in a temporal fashion to modulate neuron differentiation during brain development. Thus, modulation of neuronal CD40 isoforms and CD40 signaling may represent important therapeutic modalities for neurodegenerative and neurodevelopmental disorders, as well as, for enhancement of neurogenesis.

show abstract

Evidence for modulation of human epidermal differentiation and remodelling by CD40

Abstract: As a whole, our findings provide evidence that CD40+ keratinocytes represent a poorly differentiated population, not actively engaged in the cell cycle, which under specific stimulation is committed towards terminal differentiation.

Cited by 6 publications

References 36 publications

Kinin B2 Receptor-Coupled Signal Transduction in Human Cultured Keratinocytes

Kinin B2 Receptor-Coupled Signal Transduction in Human Cultured Keratinocytes

CD40-Mediated Amplification of Local Immunity by Epithelial Cells Is Impaired by HPV

Modulation of neuronal differentiation by CD40 isoforms

Contact Info

Product

Resources

About