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IBD (inflammatory bowel disease), where CD (Crohn's disease) and UC (ulcerative colitis) represent the two main forms, are chronic inflammatory conditions of the intestine. Macrophages play a central role in IBD pathogenesis and are regulated by major differentiation factors such as CSF-1 (colony-stimulating factor 1) in homoeostasis and inflammation. IL (interleukin)-34 has recently been discovered as a second ligand for CSF-1R (CSF-1 receptor). However, expression and involvement of IL-34 in IBD remain unknown. In the present paper, we investigated the expression of IL34, CSF1 and their shared receptor CSF1R in normal human ileum and colon, in inflamed and non-inflamed tissues of CD and UC patients, and in a mouse model of experimental colitis. We found distinct expression patterns of IL34 and CSF1 in ileum and colon, with higher IL34 in ileum and, in contrast, higher CSF1 in colon. Furthermore, IL34 and CSF1 expression was increased with inflammation in IBD patients and in experimental colitis. In humans, infiltrating cells of the lamina propria and intestinal epithelial cells expressed IL-34, and TNF-α (tumour necrosis factor α) regulated IL-34 expression in intestinal epithelial cells through the NF-κB (nuclear factor κB) pathway. These data demonstrate the expression pattern of IL-34 in ileum and colon and suggest IL-34 as a new modulator of inflammation in IBD., The macrophage differentiation factor interleukin-34, produced by intestinal epithelial cells, is up-regulated in patients with inflammatory bowel disease, and may be a novel modulator of intestinal inflammation.

COPD (chronic obstructive pulmonary disease) is caused by exposure to toxic gases and particles, most often CS (cigarette smoke), leading to emphysema, chronic bronchitis, mucus production and a subsequent decline in lung function. The disease pathogenesis is related to an abnormal CS-induced inflammatory response of the lungs. Similar to active (mainstream) smoking, second hand (sidestream) smoke exposure severely affects respiratory health. These processes can be studied in vivo in models of CS exposure of mice. We compared the acute inflammatory response of female C57BL/6 mice exposed to two concentrations [250 and 500 mg/m3 TPM (total particulate matter)] of sidestream and mainstream CS for 3 days and interpreted the biological effects based on physico-chemical differences in the gas and particulate phase composition of CS. BAL (bronchoalveolar lavage fluid) was obtained to perform differential cell counts and to measure cytokine release. Lung tissue was used to determine mRNA and protein expression of proinflammatory genes and to assess tissue inflammation. A strong acute inflammatory response characterized by neutrophilic influx, increased cytokine secretion [KC (keratinocyte chemoattractant), TNF-α (tumour necrosis factor α), MIP-2 (macrophage inflammatory protein 2), MIP-1α and MCP-1 (monocyte chemoattractant protein-1)], pro-inflammatory gene expression [KC, MIP-2 and MMP12 (matrix metalloproteinase 12)] and up-regulated GM-CSF (granulocyte macrophage colony-stimulating factor) production was observed in the mainstream model. After sidestream exposure there was a dampened inflammatory reaction consisting only of macrophages and diminished GM-CSF levels, most likely caused by elevated CO concentrations. These results demonstrate that the composition of CS determines the dynamics of inflammatory cell recruitment in COPD mouse models. Different initial inflammatory processes might contribute to COPD pathogenesis in significantly varying ways, thereby determining the outcome of the studies.

Sirtuins are members of the Sir2 (silent information regulator 2) family, a group of class III deacetylases. Mammals have seven different sirtuins, SIRT1–SIRT7. Among them, SIRT1, SIRT3 and SIRT6 are induced by calorie restriction conditions and are considered anti-aging molecules. SIRT1 has been the most extensively studied. SIRT1 deacetylates target proteins using the coenzyme NAD+ and is therefore linked to cellular energy metabolism and the redox state through multiple signalling and survival pathways. SIRT1 deficiency under various stress conditions, such as metabolic or oxidative stress or hypoxia, is implicated in the pathophysiologies of age-related diseases including diabetes, cardiovascular diseases, neurodegenerative disorders and renal diseases. In the kidneys, SIRT1 may inhibit renal cell apoptosis, inflammation and fibrosis, and may regulate lipid metabolism, autophagy, blood pressure and sodium balance. Therefore the activation of SIRT1 in the kidney may be a new therapeutic target to increase resistance to many causal factors in the development of renal diseases, including diabetic nephropathy. In addition, SIRT3 and SIRT6 are implicated in age-related disorders or longevity. In the present review, we discuss the protective functions of sirtuins and the association of sirtuins with the pathophysiology of renal diseases, including diabetic nephropathy.