human hil 19  (R&D Systems)

Journal: Cancers

Article Title: TOPK Drives IL19-Mediated Crosstalk Between Cancer Cells and Fibroblasts to Promote Solar UV-Induced Skin Damage and Carcinogenesis

doi: 10.3390/cancers17132067

Figure Lengend Snippet: TOPK drives IL19-induced cSCC growth and fibroblast activation. ( A ) Differentially expressed genes in the cytokine–cytokine receptor interaction pathway upon TOPK knockdown. The fold change and p -values of key genes are shown, with IL19 exhibiting the most significant decrease. ( B , C ) Knockdown of TOPK significantly reduced IL19 expression at the protein level and its secretion into the conditioned media (CM) of keratinocytes and cSCC cells, as determined by Western blotting. ( D ) IL19 treatment promoted cSCC A431 and SCC12 cell growth, as assessed by MTS assay. ( E ) cSCC A431 and SCC12 cells were treated with recombinant human IL19 (40 ng/mL) for 4 days. Cell growth was measured using the MTS assay. IL19 treatment significantly increased cell growth compared to untreated controls. ( F ) IL19 activated ERK, PI3K, AKT, and TOPK phosphorylation within 15 to 30 min of treatment, but this effect was not sustained at 24 h, as shown by Western blot analysis. ( G ) IL19 and αSMA expression were elevated in chronic TGFβ-treated BJ-TGFβ fibroblasts compared with normal BJ fibroblasts. ( H – K ) TOPK knockdown significantly suppressed IL19 expression and secretion in both normal BJ fibroblasts and activated BJ-TGFβ fibroblasts. ( L , M ) IL19 treatment enhanced the expression of αSMA and FAPα in normal BJ fibroblasts, as demonstrated by Western blot ( L ) and immunofluorescence staining ( M ). ( N ) The density of αSMA was obtained for each sample. Data are shown as means ± SD from three independent experiments. The asterisks indicate a significant difference compared to the group of control samples ( n = 3) (*, p < 0.05; **, p < 0.01; ***, p < 0.001 and ns: no significant difference, one-way ANOVA followed by Dunnett’s post hoc test).

Article Snippet: Human IL19 protein (10 μg, P7212) was purchased from MedChemExpress (MCE, Princeton, NJ, USA).

Techniques: Activation Assay, Knockdown, Expressing, Western Blot, MTS Assay, Recombinant, Phospho-proteomics, Immunofluorescence, Staining, Control

Journal: Cancers

Article Title: TOPK Drives IL19-Mediated Crosstalk Between Cancer Cells and Fibroblasts to Promote Solar UV-Induced Skin Damage and Carcinogenesis

doi: 10.3390/cancers17132067

Figure Lengend Snippet: TOPK/IL19 signaling crosstalk between cSCC cells and fibroblasts. In cSCC cells, TOPK activates multiple downstream pathways, including NF-κB, PI3K, ERK, p38, JNK, PKA, PKC, and PKG, which converge to promote the transcription and secretion of IL19. TOPK also enhances the expression of NFκB and IL19 in fibroblasts. Secreted IL19 promotes cSCC cell growth and acts in a paracrine manner on nearby fibroblasts, leading to their activation, as indicated by the increased expression of αSMA and FAPα. These activated fibroblasts further support cancer cell growth, suggesting a feedforward loop that drives tumor progression through IL19-mediated communication between tumor cells and the surrounding stroma.

Article Snippet: Human IL19 protein (10 μg, P7212) was purchased from MedChemExpress (MCE, Princeton, NJ, USA).

Techniques: Expressing, Activation Assay