• Journal of Life Science
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• v.24 no.6
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• pp.686-693
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• 2014

Restricted supply of nutrients may affect genes at the molecular level as well as physiological functions. Understanding the cellular responses during starvation is necessary for developing strategies to reduce damage caused by starvation stress. After 1 h of starvation, Got1 gene expression was increased but its expression returned to the normal state after 24 h. Mat1 gene expression continuously increased with starvation from 1 h until 24 hr. Rats starved for 1-3 days showed significant changes in expression of the Got1 and Mat1 genes, which were significantly reduced in the cerebral cortex and cerebellum. In the lung, gene expression was increased by starvation for 1-2 days but decreased on the third day. No differences were observed in gene expression in the heart. Strong Got1 lung gene expression was seen in the starvation group one day after restoration of the food supply. Muscle mass was significantly reduced at the start of starvation and remained the same after two days of starvation and one day after the food supply was restored. The Mat1 gene expression did not change. The Got1 was induced by NaCl and showed strong expression in the lung and the thymus, but the apparent decrease of the remaining changes were not observed in male rats. The Mat1 gene was not as sensitive as the Got1 gene to induction by NaCl. However, differences in gene induction by NaCl were evident between males and females, indicating that diet control of gene expression is associated with hormones.

• Biomedical Science Letters
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• v.2 no.2
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• pp.133-151
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• 1996

After cardiac surgery, it has been recognized that various complications were associated with injured humoral and cellular immunity by cardiopulmonary bypass(CPB). Especially, in postoperative pulmonary dysfunction, transpulmonary leukostasis followed complement activation and inflammatory responses are major pathogen. Some studies have showed that pretreated-corticosteroids before CPB protected postoperative pulmonary dysfunction. Corticosteroids may inhibit complement and leukocyte activation. On based previous studies, present investigator determined changes of leukocyte counts and transpulmonary leukostasis during cardiac surgery and postoperative periods. For the evaluation of postoperative pulmonary function and edema, $PaO_2$ and chest X-ray were compared between pre-CPB and post-CPB. Fever and other parameters were also observed postoperatively. The aim of this study was to define for the prophylactic effects of corticosteroid(Solu-Medrol: 30mg/kg) on all the researched parameters. This study was prospectively designed with randomized-blind fashion for 50 patients undergoing cardiac surgery. According to the purpose of study, all patients were divided into placebo and steroid group. : Placebo group was 25 patients received normal saline(not corticosteroid), and steroid group was 25patients received corticosteroid(Solu-Medrol: 30mg/kg) before initiation of CPB. The results of study were summarized as follows. 1. Total peripheral leukocyte counts decreased significantly at 5 minutes of CPB in all patients(P<0.01), and began to increase progressively at later periods of CPB with neutrophilia. The significant rise remained at postoperative 7th day(P<0.05). 2. During partial CPB, transpulmonary leukostasis occurred in placebo group(P<0.001), whereas it was prevented in steroid group. 3. In both groups, peripheral lymphocyte counts were stable during CPB, but began to reduce at time of intensive care unit(ICU) and the lymphocytopenia remained until postoperative 3rd day. The lymphocyte counts recovered on postoperative 7th day. 4. In both groups, peripheral counts of monocyte were relatively stable in the early peroid of CPB, and increased gradually in the later periods of CPB. This significant monocytosis remained throughout postoperlative periods(P<0.05). 5. The mean value of postoperative $paO)_2$ was lower than that of pre-CPB in placebo group(P=0.01) but didn't significant in steroid group(P=0.90). In the incidence of pulmonary edema signs and fever, placebo group was higher than steroid group(P=0.001, p=0.01, respectively). However mechanical respiratory supporting and care periods at intensive care unit were not significant difference between two groups(P>.0.05).With the above results, the investigator concluded that leukocyte activation and pulmonary sequestration were caused by cardiac surgery with CPB and demonstrated that high dose corticosteroid will provide prophylactic effect for pulmonary leukostasis and higher neutrophilia. These effects may ameliorate postoperative pulmonary dysfunction and contribute to postoperative less morbidity. However, further study should be performed because postoperative lymphocytopenia continued for 3 days in both groups, which may suspected damage or suppression of cell-mediated immunity with used corticosteroid.

• 한국유가공학회:학술대회논문집
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• 2007.09a
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• pp.49-58
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• 2007

Inflammatory process leads to the well-known mucosal damage and therefore a further disturbance of the epithelial barrier function, resulting abnormal intestinal wall function, even further accelerating the inflammatory process[1]. Despite of the records, etiology and pathogenesis of IBD remain rather unclear. There are many studies over the past couple of years have led to great advanced in understanding the inflammatory bowel disease(IBD) and their underlying pathophysiologic mechanisms. From the current understanding, it is likely that chronic inflammation in IBD is due to aggressive cellular immune responses including increased serum concentrations of different cytokines. Therefore, targeted molecules can be specifically eliminated in their expression directly on the transcriptional level. Interesting therapeutic trials are expected against adhesion molecules and pro-inflammatory cytokines such as TNF-${\alpha}$. The future development of immune therapies in IBD therefore holds great promises for better treatment modalities of IBD but will also open important new insights into a further understanding of inflammation pathophysiology. Treatment of cytokine inhibitors such as Immunex(Enbrel) and J&J/Centocor(Remicade) which are mouse-derived monoclonal antibodies have been shown in several studies to modulate the symptoms of patients, however, theses TNF inhibitors also have an adverse effect immune-related problems and also are costly and must be administered by injection. Because of the eventual development of unwanted side effects, these two products are used in only a select patient population. The present study was performed to elucidate the ability of TNF-${\alpha}$ antibodies produced in sheep colostrums to neutralize TNF-${\alpha}$ action in a cell-based bioassay and in a small animal model of intestinal inflammation. In vitro study, inhibitory effect of anti-TNF-${\alpha}$ antibody from the sheep was determined by cell bioassay. The antibody from the sheep at 1 in 10,000 dilution was able to completely inhibit TNF-${\alpha}$ activity in the cell bioassay. The antibodies from the same sheep, but different milkings, exhibited some variability in inhibition of TNF-${\alpha}$ activity, but were all greater than the control sample. In vivo study, the degree of inflammation was severe to experiment, despite of the initial pilot trial, main trial 1 was unable to figure out of any effect of antibody to reduce the impact of PAF and LPS. Main rat trial 2 resulted no significant symptoms like characteristic acute diarrhea and weight loss of colitis. This study suggested that colostrums from sheep immunized against TNF-${\alpha}$ significantly inhibited TNF-${\alpha}$ bioactivity in the cell based assay. And the higher than anticipated variability in the two animal models precluded assessment of the ability of antibody to prevent TNF-${\alpha}$ induced intestinal damage in the intact animal. Further study will require to find out an alternative animal model, which is more acceptable to test anti-TNF-${\alpha}$ IgA therapy for reducing the impact of inflammation on gut dysfunction. And subsequent pre-clinical and clinical testing also need generation of more antibody as current supplies are low.

• Tuberculosis and Respiratory Diseases
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• v.46 no.2
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• pp.215-228
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• 1999

Background: Sarcoidosis is a chronic granulomatous inflammatory disease of unknown etiology often involving the lungs and intrathoracic lymph nodes. The natural course of sarcoidosis is variable from spontaneous remission to significant morbidity or death. But, the mechanisms causing the variable clinical outcomes or any single parameter to predict the prognosis was not known. In sarcoidosis, the number and the activity of CD4 + lymphocytes are significantly increased at the loci of disease and their oligoclonality suggests that the CD4 + lymphocytes hyperreactivity may be caused by persistent antigenic stimulus. Recently, it has been known that CD4+ lymphocytes can be subdivided into 2 distinct population(Th1 and Th2) defined by the spectrum of cytokines produced by these cells. Th1 cells promote cellular immunity associated with delayed type hypersensitivity reactions by generating IL-2 and IFN-$\gamma$. Th2 cells playa role in allergic responses and immediate hypersensitivity reactions by secreting IL-4, IL-5, and IL-10. CD4+ lymphocytes in pulmonary sarcoidosis were reported to be mainly Th1 cells. IL-12 has been known to play an important role in differentiation of undifferentiated naive T cells to Th1 cells. And, Moller et al. observed increased IL-12 in bronchoalveolar lavage fluid(BALF) in patients with sarcoidosis. So it is possible that the elevated level of IL-12 is necessary for the continuous progression of the disease in active sarcoidosis. This study was performed to test the assumption that IL-12 can be a marker of active pulmonary sarcoidosis. Methods: We measured the concentration of IL-12 in BALF and in conditioned medium of alveolar macrophage(AM) using ELISA(enzyme-linked immunosorbent assay) method in 26 patients with pulmonary sarcoidosis(10 males, 16 females, mean age: $39.8{\pm}2.1$ years) and 11 normal control. Clinically, 14 patients had active sarcoidosis and 12 patients had inactive. Results: Total cells counts, percentage and number of lymhocytes, number of AM and CD4/CD8 lymphocyte ratio in BALF were significantly higher in patients with sarcoidosis than in control group. But none of these parameters could differentiate active sarcoidosis from inactive disease. The concentration of IL-12 in BALF was significantly increased in sarcoidosis patients ($49.3{\pm}9.2$ pg/ml) than in normal control ($2.5{\pm}0.4$ pg/ml) (p<0.001). Moreover it was significantly higher in patients with active sarcoidosis ($70.3{\pm}14.8$ pg/ml) than in inactive disease ($24.8{\pm}3.l$ pg/ml) (p=0.001). Also, the concentration of IL-12 in BALF showed significant correlation with the percentage of AM(p<0.001), percentage(p<0.001) and number of lymphocyte(p<0.001) in BALF, suggesting the close relationship between the level of IL-12 in BALF and the inflammatory cell infiltration in the lungs. Furthermore, we found a significant correlation between the level of IL-12 and the concentration of soluble ICAM-1 : in serum(p<0.001) and BALF (p=0.001), and also between IL-12 level and ICAM-1 expression of AM(p<0.001). The AM from patients with pulmonary sarcoidosis secreted significantly larger amount of IL-12 ($206.2{\pm}61.9$ pg/ml) than those of control ($68.3{\pm}43.7$ pg/ml) (p<0.008), but, there was no difference between inactive and active disease group. Conclusion : Our data suggest that the BALF IL-12 level can be used as a marker of the activity of pulmonary sarcoidosis.