Interleukin‐1α regulates antimicrobial peptide expression in human keratinocytes

Abstract

Human epidermis and epithelium serve as physiologic barriers to protect against noxious and infectious agents. Contributing to the defense against infection, epithelial cells express antimicrobial peptides (AMPs). The expression of AMPs in keratinocytes is generally regulated directly by bacteria and indirectly by proinflammatory cytokines. Bacteria may also regulate AMP expression by inducing keratinocyte expression of the autonomous proinflammatory cytokine, interleukin-1a (IL-1a). To test the hypothesis that AMP expression may be regulated by cell autonomous cytokines, we investigated the effect of IL-1a on the expression of AMPs in human keratinocytes (HaCaT cells) by microarray, northern blot, reverse transcriptase (RT)-PCR and western blot analyses. IL-1a increased expression of mRNA in a dose-and time-dependent manner specific for lipocalin 2, S100A8, S100A9 and secretory leukocyte protease inhibitor (SLPI) more than twofold relative to nonstimulated cells (control), and slightly upregulated S100A7 and b-defensin-2. Furthermore, the expression of lipocalin 2, S100A7, S100A8, S100A9 and SLPI proteins were upregulated by IL-1a. On the other hand, HaCaT cells expressed mRNA specific for other AMPs, including cystatin 3, adrenomedullin, RNase-7 and mucin 5, which were unaffected by IL-1a treatment. These results suggest that the autonomous keratinocyte cytokine, IL-1a, selectively upregulates the expression of AMPs which may modulate innate epithelial cell immunity in skin and mucosa.

α–Intercalated cells defend the urinary system from bacterial infection

“…These included LPS (lipid A), which we previously found to powerfully induce high levels of LCN2 in the kidney medulla (15), and Ent, which we found to induce uLCN2 and kidney Lcn2 message (2.8 ± 0.68-fold; n = 5; P = 0.037 at 6 hours; Supplemental Figure 4), consistent with cytokine activation by Ent in other models (78). The UPEC inoculum in C57BL/6 mice also induced kidney cytokines (e.g., Il1a, Il18, and Cxcl1; n = 10; Figure 4G), some of which are known to amplify LCN2 expression (79)(80)(81). These data indicated that urinary bacteria might induce uLCN2 with a variety of ligands.…”

“…To determine whether TLR4 regulates additional genes, we measured the same cytokines that UPEC induced in the C57BL/6 kidney (e.g., Il1a and Il1b, Figure 5C). C57BL/6 and C3H Lps n kidneys expressed a similar profile of cytokine responses to UTI, but the Lps d mouse severely blunted their expression (n = 15 and 9, respectively, P < 0.05, Figure 9D) (79)(80)(81). To determine whether the Lps d phenotype could be ascribed to TLR4 expression in the kidney parenchyma, we transplanted Lps n kidneys into nephrectomized Lps d hosts and vice versa, and treated the recipients with LPS (1 mg/kg i.p.).…”

S100A7 (psoriasin) is induced by the proinflammatory cytokines oncostatin-M and interleukin-6 in human breast cancer

“…Nevertheless, in nonneoplastic skin pathologies, several investigators have reported S100A7 induction in response to inflammatory cytokines, including OSM, IL-1, IL-17, IL-20 and IL-22 (Boniface et al, 2005;Gazel et al, 2006;Liang et al, 2006;Wolk et al, 2006;Bando et al, 2007;Boniface et al, 2007;Sa et al, 2007). Each of these cytokines has the capacity to signal, either directly or indirectly, through STAT3, ERK1/2 and PI3K (Heinrich et al, 2003;Pestka et al, 2004;Gaffen, 2008;Perrier et al, 2008).…”

Calprotectin in rheumatic diseases

“…It has been found in renal tissue from SLE patients with glomerulonephritis, especially with proliferative lesions, and in the epidermis where it is produced by keratinocytes lesions. 4,44,115 Skin stressors, including UV exposure, 116 lead to an inflammatory response, which is usually part of the physiological mechanism of wound healing, but might also be responsible for autoimmune disregulation in skin lesions. 21 Patients with SLE have higher serum CLP levels compared with healthy individuals and also SS patients.…”