IFN-[gamma] (a), TNF-[alpha] (b), GM-CSF (c), CCL3 (d), IL-17 (e), CCL5
(f), IL-4 (g), and CCL4 (h) secretion from in vitro stimulated [CD4.sup.+] T cells.
CXCL10, CCL2, CCL5
G-CSF, and GM-CSF are in the chemoattractant and proliferation signal group.
These 27 SNPs in 12 chemokine genes, included 4 SNPs (rs1024610, rs1024611, rs13900, and rs4586) of CCL2 [21, 22], 5 SNPs (rs4251719, rs2306630, rs2107538, rs9355610, and rs2280788) of CCL5
[12, 23, 24], 1 SNP (rs854680) of CCL16 , 2 SNPs (rs223828 and rs223895) of CCL17 [26-28], 3 SNPs (rs951005, rs2492358, and rs2812378) of CCL21 [29-31], 1 SNP (rs4359426) of CCL22 , 2 SNPs (rs2302004 and rs2302005) of CCL24 , 3 SNPs (rs2227306, rs2227543, and rs4694178) of CXCL8 , 2 SNPs (rs2276886 and rs2869460) of CXCL9 [14, 35], 1 SNP (rs2869462) of CXCL10 , 2 SNPs (rs1801157 and rs2839693) of CXCL12 [13, 15], and 1 SNP (rs2277680) of CXCL16 .
RANTES, a member of the C-C or [sz] chemokine subfamily, is classified as CCL5
[sup] and expressed in activated T-lymphocytes, airway epithelial cells, platelets, fibroblasts, and renal epithelial and mesangial cells.
Indeed, in the past we have shown in skin equivalents with integrated Langerhans Cells (SE-LC) that upon allergen exposure MUTZ-3 LC mature and migrate in a CXCL12 dependent manner from the epidermis to the dermis, whereas upon irritant exposure MUTZ-3 LC migrate in a CCL5
dependent manner and undergo an IL-10 dependent phenotypic switch into a macrophage-like cell in the dermis, closely mimicking our observations in excised skin (Kosten et al., 2015b; Ouwehand et al., 2008, 2011b).
At the molecular level, inflammation can be measured by the expression of inflammatory transcription factors (e.g., NF-[kappa]B, AP-1, STAT3), inflammatory enzymes (e.g., COX2, MMP-9, PPAR), inflammatory cytokines (e.g., IL-6, IL-8, and TNF-[alpha]), and chemokines (CCL3, CCL4, CCL5
(28) Damaged neurons also produce IFN-[gamma], IL1, IL6, IL12, CCL2, CCL4, CCL5
, CCL7 and the IFN-inducible protein, CXCL10.
Los factores de transcripcion activados se traslocan del citoplasma al nucleo, donde se unen a los promotores de sus genes blanco (IFNs, TNF, AIP3, CXCL10, CCL5
, SElE, IFIT1-IFIT2) e inducen su transcripcion.
Validacion por qRT-PCR de la expresion de genes seleccionados Para validar los datos obtenidos con los microarreglos, se realizo qRT-PCR para un grupo de 10 genes, incluyendo las quimiocinas proinflamatorias (CCL2, IL8, CCL5
, CCL18), moleculas efectoras involucradas en los mecanismos de muerte celular dependiente de celulas T citotoxicas (cistatina B, granzima B, granulisina), y metalotioneinas (1H, 1M, 1G).
CCL3 (chemokine ligand 3, also known as macrophage inflammatory protein-1a), CCL4 (macrophage inflammatory protein-1b) and CCL5
(also known as RANTES--regulated on activation normal T cell expressed and secreted) .
In aging mice, at the mRNA level, several genes specific for T cells (CD3, CD8, T cell receptor, and LY75), antigen presentation ([beta]2-microglobulin and H2 molecules), T lymphocytes chemotaxis (CXCL9, CXCL10, CXCL11, and CCL5
), and adhesion of leucocytes (ICAM-1) were overexpressed in the RPE/choroid complex and the retina [67, 68].
They also contribute to the immune regulation of the skin, producing and releasing chemokines IL-8 and CCL5
, cyclooxygenases, and prostanoids, after activation by inflammatory agents, such as bacterial agents .