CCL13
C-C motif chemokine 13 precursor (CK-beta-10) (Monocyte chemoattractant protein 4) (Monocyte chemotactic protein 4) (MCP-4) (NCC-1) (Small-inducible cytokine A13) [Contains: C-C motif chemokine 13, long chain; C-C motif chemokine 13, medium chain; C-C motif chemokine 13, short chain] [MCP4] [NCC1] [SCYA13]
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Atopic dermatitis (AD) shows differential clinical presentation in older compared with younger patients. Nevertheless, changes in the AD molecular profile with age are unknown. We sought to characterize age-related changes in the AD profile. We evaluated age-specific changes in lesional and nonlesional tissues and blood from patients with moderate-to-severe AD (n = 246) and age-matched control subjects (n = 71) using immunohistochemistry, quantitative real-time PCR, and Singulex in a cross-sectional study. Patients were analyzed by age group (18-40, 41-60, and ≥61 years). Although disease severity/SCORAD scores were similar across AD age groups (mean, approximately 60 years; P = .873), dendritic cell infiltrates (CD1b and FcεRI , P < .05) decreased with age. T 2 measures (IL5, IL13, CCL13, CCL18, and CCL26) significantly decreased with age in patients with AD, despite increasing with age in control subjects. Consistent with T 2 axis decreases, serum IgE levels and eosinophil counts negatively correlated with age in patients with AD (r = -0.24 and r = -0.23, respectively; P < .05). T 22-secreted IL22 expression levels also decreased with age uniquely in patients with AD (P < .05). Expression of T 1-related (IFNG, IL12/23p40, STAT1, and CXCL9; P < .05 for CXCL9) and T 17-related (IL17A and IL20; P < .05 for IL20) markers increased with age in both patients with AD and control subjects. Expression of terminal differentiation measures significantly increased in older patients with AD (loricrin [LOR] and filaggrin [FLG], P < .05), whereas expression of S100As (S100A8, P < .01) and hyperplasia markers (epidermal thickness, keratin 16, and Ki67; P < .05 for keratin 16) decreased. Serum trends in AD mimicked skin findings, with T 2 downregulation (CCL26; r = -0.32, P < .1) and T 1 upregulation (IFN-γ; r = 0.48, P < .01) with age. The adult AD profile varies with age. Although T 1/T 17 skewing increases in both patients with AD and control subjects, patients with AD show unique decreases in T 2/T 22 polarization and normalization of epithelial abnormalities. Thus age-specific treatment approaches might be beneficial for AD.
MeSH Terms
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Aging
- Cytokines
- Dermatitis, Atopic
- Female
- Gene Expression
- Humans
- Male
- Middle Aged
- Phenotype
- Severity of Illness Index
- Skin
- Young Adult
Keywords
- Atopic dermatitis
- T(H)1
- T(H)17
- T(H)2
- T(H)22
- aging
- biomarker
- filaggrin
- hyperplasia
- loricrin
- skin
Recent evidence has determined a phenotypic and functional heterogeneity for macrophage populations. This plasticity of macrophage function has been related to specific properties of subsets (M1 and M2) of these cells in inflammation, adaptive immune responses and resolution of tissue destructive processes. This investigation hypothesized that targeted alterations in the distribution of macrophage phenotypes in aged individuals, and with periodontitis would be skewed towards M1 inflammatory macrophages in gingival tissues. The study used a non-human primate model to evaluate gene expression profiles as footprints of macrophage variation in healthy and periodontitis gingival tissues from animals 3-23 years of age and in periodontitis tissues in adult and aged animals. Significant increases in multiple genes reflecting overall increases in macrophage activities were observed in healthy aged tissues, and were significantly increased in periodontitis tissues from both adults and aged animals. Generally, gene expression patterns for M2 macrophages were similar in healthy young, adolescent and adult tissues. However, modest increases were noted in healthy aged tissues, similar to those seen in periodontitis tissues from both age groups. M1 macrophage gene transcription patterns increased significantly over the age range in healthy tissues, with multiple genes (e.g. CCL13, CCL19, CCR7 and TLR4) significantly increased in aged animals. Additionally, gene expression patterns for M1 macrophages were significantly increased in adult health versus periodontitis and aged healthy versus periodontitis. The findings supported a significant increase in macrophages with aging and in periodontitis. The primary increases in both healthy aged tissues and, particularly periodontitis tissues appeared in the M1 phenotype.
MeSH Terms
- Age Factors
- Aging
- Animals
- Disease Models, Animal
- Female
- Gene Expression Profiling
- Gene Expression Regulation
- Gingiva
- Macaca mulatta
- Macrophage Activation
- Macrophages
- Male
- Periodontitis
- Transcriptome
Keywords
- Aging
- gene expression
- gingival tissue
- macrophage polarization
- periodontitis
Ionizing radiation has been demonstrated to result in degranulation of dermal mast cells. Chemokines are thought to play a crucial role in the early phase of the cutaneous radiation reaction. In human skin, mast cells are located in close proximity to dermal fibroblasts, which thus are a potential target for the action of mast cell mediators. In this study, we evaluated the effects of mast cell-derived histamine, serotonin, tumour necrosis factor (TNF)-α and tryptase on chemokine release from dermal fibroblasts. Human mast cells (HMC-1) were investigated for histamine release and cytokine production after ionizing radiation using enzyme-linked immunosorbent assay (ELISA) and flow cytometry. Receptor expression on human fetal foreskin fibroblasts (HFFF2) and human adult skin fibroblasts (HDFa) was examined by flow cytometry. Chemokine mRNA and protein expression were analyzed by gene array and ELISA, respectively. Ionizing radiation significantly increased histamine release and cytokine expression by HMC-1 cells. Receptors for histamine, serotonin, TNF-α and tryptase were detected both in HFFF2 and in HDFa cells. Dermal fibroblasts constitutively expressed distinct sets of chemokine mRNA. Mast cell mediators differentially affected the release of chemokines CCL8, CCL13, CXCL4 and CXCL6 by fibroblasts. Our data suggest that radiation-induced mast cell mediators have a tremendous impact on inflammatory cell recruitment into irradiated skin. We postulate the activation of mast cells to be an initial key event in the cutaneous radiation reaction, which might offer promising targets for treatment of both normal tissue side effects in radiation therapy and radiation injuries.
MeSH Terms
- Aging
- Cell Communication
- Cell Line
- Cells, Cultured
- Chemokines
- Cytokines
- Dermis
- Fibroblasts
- Histamine
- Humans
- Mast Cells
- Serotonin
- Tryptases
- Tumor Necrosis Factor-alpha