Surface TLR2 and TLR4 expression on mature rat mast cells can be affected by some bacterial components and proinflammatory cytokines.

The aim of our study was to determine whether some bacterial components as well as some proinflammatory cytokines can affect surface mast cell levels. By the use of flow cytometry technique, we documented that freshly isolated mature rat peritoneal mast cells do express surface TLR2 and TLR4 protein, but not CD14 molecules, and respond to stimulation with TLR2 and TLR4 ligands by cysteinyl leukotriene generation. The level of TLR2 protein is modulated by PGN and CCL5 treatment, but not by LPS, LAM, TNF, or IL-6. Surface mast cell TLR4 expression is affected by LPS, LAM, IL-6, and CCL5. Considering that TLR-mediated activation conditions not only engaged these cells in antibacterial defense and development of inflammation but also might influence allergic processes, our observations that surface TLR2 and TLR4 expression can be regulated both bacterial components and proinflammatory cytokines seem to be very intriguing and importance.

Diverse effects of bacterial cell wall components on mast cell degranulation, cysteinyl leukotriene generation and migration.

Nowadays there is more and more evidence that mast cells take part in antibacterial defence. Mast cells have the ability to kill bacteria via phagocytose-dependent or phagocytose-independent ways and express antimicrobial peptides that can directly kill pathogens at their site of entry. What is more, mast cells are capable of processing bacterial antigens for presentation through class I and II MHC molecules. Some data indicate that these cells can release various proinflammatory mediators in response to activation with bacteria and/or their products, however this information is still far from complete. Therefore, in this study we examined the ability of PGN from Staphylococcus aureus, LPS from Eschericha coli and LAM from Mycobacterium smegmatis to stimulate mature rat mast cell degranulation as well as cysteinyl LT generation. We also studied the influence of these bacterial components on mast cell migration. We found that PGN, LPS and LAM all failed to induce mast cell degranulation and histamine release. At the same time, activation of mast cells with these bacterial antigens resulted in generation and release of significant amounts of LT. Moreover, we documented that, even in the presence of laminin, none of the bacterial antigens used stimulated mast cell migration. However, PGN did induce migration of RANTES-primed mast cells, and LPS did stimulate mast cell migratory response after priming with IL-6. Our results show that PGN, LPS and LAM might be among the important bacterial antigens involved in mast cell activation during bacterial infection.

[Role of transforming growth factor beta1 (TGF-beta1) in the pathogenesis and clinical course of chronic hepatitis in children]. / Rola transformujacego czynnika wzrostu beta1 (TGF-beta1) w etiopatogenezie i przebiegu klinicznym przewleklych zapalen watroby u dzieci.

UNLABELLED: Transforming growth factor-beta1 (TGF-beta1) is known to play a key role in processes of cell proliferation and differentiation. It also plays an important role in modulation of the immune response. Various diseases may arise both from excessive and insufficient activity of this cytokine. THE AIM OF THE STUDY was to evaluate the role of TGF-beta1 in the pathogenesis of chronic hepatitis (Ch.h.) and to assess whether TGF-beta1 level in plasma or its tissue expression can be useful in diagnosing and monitoring of clinical course of this disease. PATIENTS AND METHODS: Twenty-one children with chronic hepatitis were included in the study and 42 healthy children constituted the control group. Liver function tests and TGF-beta1 plasma levels measured by ELISA method were evaluated in both groups of patients. In liver tissue obtained by needle biopsy, the histopathological grading and staging of hepatitis was evaluated, TGF-beta1 protein was assessed by immunohistochemical methods and TGF-beta1 gene expression was measured by reverse transcription and real-time polymerase chain reaction. RESULTS: In chronic hepatitis group of patients the plasma TGF-beta1 level did not differ from the control group and did not correlate with grading and staging of the liver tissue while positive correlation was observed with gamma-glutamyl transpeptidase activity in the serum. There was no correlation between tissue TGF-beta1 expression and TGF-beta1 plasma level and staging or grading in liver tissue. TGF-beta1 gene expression correlated positively with ESR and ALAT activity but no correlation with TGF-beta1 plasma level, TGF-beta1 gene or protein expression, grading or staging in liver tissue were observed. CONCLUSION: 1. In children with chronic hepatitis, TGF-beta1 plasma level is not related to grading or staging in the liver tissue. This finding may be due to low level of fibrosis observed in the studied children. 2. It appears that local expression of TGF-beta1 in liver tissue should not be used as a sole marker in differentiating and monitoring the course of chronic hepatitis. 3. In children with chronic hepatitis assessment of liver TGF-beta1 gene expression is not helpful in the evaluation of pathological changes in liver tissue. 4. Due to the relatively low number of patients in the analysed groups it seems advisable to perform similar complex studies in larger groups of children with chronic hepatitis.

[The role of mast cells in the development of inflammatory bowel diseases]. / Rola komórek tucznych w rozwoju przewleklych nieswoistych zapalen jelit.

The pathomechanism of inflammatory bowel disease (IBD), i.e. Crohn's disease and ulcerative colitis, is not well understood. There is growing evidence that mast cells take part in the course of these diseases. It is well known that mast cells are numerous in the gastrointestinal tract. What is more, the number of mast cells increases in intestinal tissues in IBD. Mast cells release several mediators, cytokines, and chemokines that can influence the inflammatory process in the gastrointestinal tract in various ways. One mediator that plays a very important role in the development of IBD is tumor necrosis factor (TNF). Other mast cell-derived cytokines and chemokines also seem to be involved in the development of intestinal inflammation. Moreover, some unique mast cell mediators, such as histamine, tryptase, and chymase, play crucial roles in the course of IBD. Finally, there is some data showing that mast cell-derived metalloproteinases (especially MMP-9), leukotrienes (LTs), platelet activating factor (PAF), and heparin take part in inflammation during IBD. It seems that current data about the role of mast cell-derived mediators and cytokines in IBD should be taken into consideration when new approaches to treating these diseases are being introduced.