In naturally occurring bovine mastitis, effects of infection depend on the host inflammatory response, including the effects of secreted cytokines. Knowledge about the inflammatory and regulatory cytokines in milk cells of free-stall barn dairy cows and in naturally occurring mastitis is lacking as most studies focus on induced mastitis. Hereby, the aim of the study was to determine inflammatory and regulatory cytokines in the milk of dairy cows with subclinical and clinical mastitis. The following examinations of milk samples were performed: differential counting of somatic cells (SCC), bacteriological examination, and immunocytochemical analysis. Mean SCC increased in subclinical and clinical mastitis cases. The number of pathogenic mastitis-causing bacteria on plates increased in subclinical mastitis cases but decreased in clinical mastitis. The inflammatory and regulatory markers in the milk cells of healthy cows showed the highest mean cell numbers (%). In mastitis cases, immunoreactivity was more pronounced for IL-4, IL-6, IL-12, IL-13, IL-17A, TNF-α, and IFN-γ. Data about subclinical and clinical mastitis demonstrate inflammatory responses to intramammary infection driven by IL-1α, IL-4, and IL-17A. Moreover, the host defense response in mastitis is characterized by continuation or resolution of initial inflammation. IL-12 and INF-γ immunoreactivity was recognized to differ mastitis cases from the relative health status.

Background and Objectives: Intercellular signaling networks with high complexity cause a spectrum of mechanisms achieving chronic obstructive pulmonary disease (COPD) that still question many uncertainties. Materials and Methods: Immunoreactive cells in bronchial tissue obtained from 40 COPD patients and 49 healthy control subjects were detected by biotin-streptavidin immunohistochemistry method for the following markers of IL-1α, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12, TNF-α, MMP-2, TIMP-2, TGF-β1, Hsp−70, hBD−2, hBD−3, hBD−4. Results: Overall the highest numbers (from mostly moderate (++) to abundance (++++)) of IL-1α, IL-4, IL-7, IL-8, IL-10, IL-12, MMP-2, TIMP-2, TGF-β1 immunoreactive cells were marked increasingly in the blood vessel wall, connective tissue, and bronchial epithelium of COPD-affected lung, respectively. We found statistically significant (p < 0.05) higher numbers of immunoreactive cells positive for all of examined interleukins, TNF-α, MMP-2, TIMP-2, TGF-β1, hBD-2, and hBD-3 in the COPD-affected lung compared to the control group, but not for Hsp-70 and hBD-4. Conclusions: COPD-affected lung tissue exhibits mostly inflammatory response patterns of increased IL-1α, IL-4, IL-8, IL-12, and TNF-α, especially in the airway epithelium. Increased MMP-2 and TGF-β1, but decreased Hsp-70, proposes pronounced tissue damage and remodeling in COPD. High numbers of hBD-2 and hBD-3 immunoreactive cells may highlight antimicrobial activity in COPD within stable regulation of local immunity.

Lung tissue remodeling requires complex interactions of matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), transforming growth factor (TGF) family and heat shock protein 70 (Hsp70). We evaluated the appearance and distribution of MMP-2, TIMP-2, TGF-β1 and Hsp70 in lung tissue using immunohistochemistry. Stained structures were graded semiquantitatively. Overall, more MMP-2, TIMP-2, TGF-β1 and Hsp70 were observed in bronchial cartilage, bronchial and alveola repithelium, and among alveolar macrophages. We evaluated mostly alveolar macrophages, bronchial epithelial cells and mucosal fibroblasts stained for TGF-β1, MMP-2 and TIMP-2. We also assessed strong or moderate correlations between numbers of cells containing TGF-β1, MMP-2, TIMP-2 in patients ≥ 60 years old. The presence of less TGF-β1 and more MMP-2, TIMP-2 and Hsp70 containing cells in all tissue groups indicated that local regulation was more dependent on MMP-2, TIMP-2 and Hsp70 distribution. Fewer TIMP-2, Hsp70 and TGF-β1 immunoreactive cells in younger individuals and increased expression of Hsp70 in elderly individuals demonstrated the influence of aging in lung remodeling. Findings of MMP-2, TIMP-2 and TGF-β1 immunoreactive cells in elderly individuals indicate lung remodeling due to aging.

Orofacial clefts affect hundreds of thousands of children worldwide annually and are usually corrected by a series of surgeries extending to childhood. The underlying mechanisms that lead to clefts are still unknown, mainly because of the multifactorial etiology and the myriad of interactions between genes and environmental factors. In the present study, we investigated the role and expression of candidate genes belonging to the FGF/FGFR signaling pathway and FOX family in tissue material obtained from 12 pediatric patients undergoing cleft correction surgery. The expression was investigated using immunohistochemistry (IHC) and chromogenic in-situ hybridization (CISH) in three cell/tissue types—epithelial cells, connective tissue, and endothelial cells. We found elevated expression of FGFR1 in epithelial cells while no expression was observed in endothelial cells. Further, our results elucidate the potential pathogenetic role of FGFR1 in cellular proliferation, local site inflammation, and fibrosis in cleft patients. Along with bFGF (also called FGF2), FGFR1 could play a pro-inflammatory role in clefts. Over-amplification of FGFR2 in some patients, along with bFGF, could potentially suggest roles for these genes in angiogenesis. Additionally, increased expression of FOXE1 (also called TTF2) contributes to local site inflammation. Finally, zero to low amplification of FOXO1 could suggest its potential role in inducing oxidative stress in the endothelium along with reduced epithelial apoptosis.

Background: The innate and adaptive immune systems in lungs are maintained not only by immune cells but also by non-immune tissue structures, locally providing wide intercellular communication networks and regulating the local tissue immune re...