[논문]Jurkat T 림프구와 U937 단핵구에서 중성지방 처리 시 iNOS를 통한 염증성 사이토카인의 mRNA 발현 증가

장정현

doi:10.7742/jksr.2019.13.1.133

Jurkat T 림프구와 U937 단핵구에서 중성지방 처리 시 iNOS를 통한 염증성 사이토카인의 mRNA 발현 증가
Triglycerides increase mRNA Expression of Pro-inflammatory Cytokines Via the iNOS in Jurkat T lymphocyte and U937 Monocyte Cell Lines 원문보기

한국방사선학회 논문지 = Journal of the Korean Society of Radiology, v.13 no.1, 2019년, pp.133 - 140

초록
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중성지방(Triglyceride, TG)는 죽상동맥경화증과 같은 혈관의 만성 염증성 병변을 유발하는 인자 중 하나이다. 종양괴사인자-알파 ($TNF-{\alpha}$), 인터루킨-1 베터 ($IL-1{\beta}$)와 같은 염증성 사이토카인은 염증 질환의 주요 요인으로 염증 부위에 T 림프구, 단핵구등의 면역 세포의 침윤을 유도하거나 세포 및 조직 괴사를 일으킴으로써 질병을 더욱 악화시킨다. 본 연구에서는 혈관 염증에 관여하는 Jurkat T 림프구와 U937 단핵구에 TG를 처리하였을 때 $TNF-{\alpha}$와 $IL-1{\beta}$의 발현에 미치는 영향을 조사하고자 했다. Jurkat T 세포에서 TG에 의해 $TNF-{\alpha}$의 mRNA 발현이 증가하였고, U937 단핵구에서는 TG에 의해 $TNF-{\alpha}$와 $IL-1{\beta}$ 모두 mRNA 발현이 증가하였다. 또한 유도성 산화질소합성효소(inducible nitric oxide synthase, iNOS)가 TG에 의한 $TNF-{\alpha}$와 $IL-1{\beta}$의 발현 증가에 관여하는지 확인하기 위해 iNOS 억제제인 W1400을 세포에 전처리하여 iNOS의 활성을 차단하였다. 그 결과, W1400을 전처리한 세포에서는 TG에 의한 $TNF-{\alpha}$ 및 $IL-1{\beta}$ mRNA 양이 대조군과 유사하게 낮은 수준으로 관찰되었다. 이는 혈관 내 TG의 증가가 T 림프구와 단핵구를 자극하여 iNOS 신호를 거쳐 염증성 사이토카인을 분비시키고 혈관염증질환을 발생하는데 관여하는 것을 확인시켜주었다. 결론적으로, 중성지방이 염증성 병변을 악화시키는데 있어 iNOS의 활성이 사이토카인 분비 등에 작용하며 병변을 더욱 악화시키는데 기여할 수 있다. 반면, iNOS 발현을 조절하여 고지혈증 환자의 치료에 유효한 표적 물질로 이용될 가능성이 있다고 사료된다.

Abstract ▼ AI-Helper

Triglycerides (TG) are one of the triggers of chronic inflammatory lesions in the blood vessels. In the key factors in the development of inflammatory diseases, Pro-inflammatory cytokines such as tumor necrosis factor-alpha $(TNF-){\alpha}$ and interleukin-1 beta ($IL-1{\beta}$) contribute to the development of inflammatory lesions by recruiting other immune cells in the inflamed area or causing cell necrotic death. In this study, I investigated the effect of Jurkat T lymphocytes and U937 monocytes involved in vascular inflammation development on the expression of $TNF-{\alpha}$ and $IL-1{\beta}$ on exposure to TGs. In Jurkat cells, mRNA expression of $TNF-{\alpha}$ is increased by exposure to TGs. However, the expression levels of $TNF-{\alpha}$ and $IL-1{\beta}$ were increased by TGs in U937 cells. To investigate whether inducible nitric oxide synthase (iNOS) is involved in the increase of expression of $TNF-{\alpha}$ and $IL-1{\beta}$ by TGs, treatment of W1400 (an iNOS inhibitor) resulted in recovery of expression level both $TNF-{\alpha}$ and $IL-1{\beta}$. Based on the present study, it was confirmed that the expression of $TNF-{\alpha}$ and $IL-1{\beta}$ in monocytes and T lymphocytes. This increased cytokines contribute to development of vascular inflammatory lesions. In addition, iNOS is involved in the increase of $TNF-{\alpha}$ and $IL-1{\beta}$ expression by TGs.

주제어

표/그림 (7)

그림 Fig. 1. RT-PCR for detection of TNF-α mRNA expression in the Jurkat T lymphocytes.
그림 Fig. 2. RT-PCR for detection of IL-1β mRNA expression in the Jurkat T lymphocytes.
그림 Fig. 3. RT-PCR for detection of TNF-α mRNA expression in the U937 cells.
그림 Fig. 4. RT-PCR for detection of IL-1β mRNA expression in the U937 cells.
그림 Fig. 5. RT-PCR for detection of TNF-α mRNA expression in the Jurkat T lymphocytes pretreatedwith iNOS inhibitors.
그림 Fig. 6. RT-PCR for detection of TNF-α mRNA expression in the U937 cell pretreated with iNOS inhibitors.
그림 Fig. 7. RT-PCR for detection of IL-1β mRNA expression in the U937 cell pretreated with iNOS inhibitors.

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가설 설정

Although previous studies have shown that TG is involved in the death of inflammatory cells and secretion of cytokines, there is no known correlation with iNOS. In this study, I determined the effects of triglyceride, which is involved in the development of chronic inflammatory diseases in blood vessel, on the expression of inflammatory cytokines-secreted by T cell and mononuclear cells. I then investigated the pathogenesis of atherosclerosis by TG.

제안 방법

In order to investigate the effect of TGs on mRNA expression of TNF-α and IL-1β, pro-inflammatory cytokines that are deeply involved in the inflammatory response, TGs were treated to Jurkat T lymphocytesin a concentration-dependent and time-dependent manner.

대상 데이터

TRIzol® for RNA isolation was obtained from Invitrogen (Carlsbad, CA, USA). Chemical inhibitors for iNOS (W1400) and dimethyl sulfoxide(DMSO) were obtained from Sigma-Aldrich (St. Louis, MO, USA). The iNOS inhibitor was dissolved as stock solutions in DMSO and stored at -20°C prior to usage.

데이터처리

Statistical analysis was performed using GraphPad Prism 5 (GraphPad Software Inc., San Diego, CA, USA). p-values were calculated using Student’s t-test.
p-values were calculated using Student’s t-test.

성능/효과

These results showed that the mRNA expression of IL-1β as well as TNF-α was increased when U937 monocyte was exposed to TGs.

후속연구

Therefore, it is believed that there is no problem in predicting the result even with mRNA detection. Of course, once theiNOS-related TG mechanism has been identified as awhole, it will proceed with further research to directly identify the proteins associated with genes.

참고문헌 (23)

R. Krysiak, B. Okopien, "Monocyte-suppressing effects of simvastatin in patients with isolated hypertriglyceridemia," European journal of internal medicine, Vol. 24, No. 3, pp. 255-259, 2013.

상세보기
W. P. Castelli, "Epidemiology of triglycerides: a view from Framingham," The American journal of cardiology, Vol. 70, No. 19, pp. 3H-9H, 1992.

상세보기
M. J. Malloy, J. P. Kane, "A risk factor for atherosclerosis: triglyceride-rich lipoproteins," Advances in internal medicine, Vol. 47, No. 1, pp. 111-136, 2001.
D. Burger, J. M. Dayer, "The role of human T-lymphocyte-monocyte contact in inflammation and tissue destruction," Arthritis research, Vol. 4, No. Suppl 3, pp. S169-176, 2002.

상세보기
G. S. Firestein, N. J. Zvaifler, "How important are T cells in chronic rheumatoid synovitis?: II. T cell-independent mechanisms from beginning to end," Arthritis and rheumatism, Vol. 46, No. 2, pp. 298-308, 2002.

상세보기
P. Lsler, E. Vey, J. H. Zhang, J. M. Dayer, "Cell surface glycoproteins expressed on activated human T-cells induce production of interleukin-1 beta by monocytic cell: a possible role of CD69," European Cytokine Network, Vol. 4, No. 1, pp. 15-23, 1993.
S. Lacraz, P. Isler, E. Vey, H. G. Welgus, J. M. Dayer, "Direct contact between T lymphocytes and monocytes is a major pathway for induction of metalloproteinase expression," The Journal of Biological Chemistry, Vol. 269, No. 35, pp. 22027-22033, 1994.

상세보기
E. Vey, D. Burger, J. M. Dayer, "Expression and cleavage of tumor necrosis factor-alpha and tumor necrosis factor receptors by human monocytic cell lines upon direc contact with stimulated T cells," European Journal of Immunology, Vol. 26, No. 10, pp. 2404-2409, 1996.

상세보기
J. M. Li, P. Isler, J. M. Dayer, D. Burger, "Contact-dependent stimulation of monocytic cells and neutrophils by stimulated human T-cell clones," Immunology, Vol. 84, No. 4, pp. 571-576, 1995.

상세보기
V. E. Stoneman, M. R. Bennett, "Role of apoptosis in atherosclerosis and its therapeutic implications," Clinical Science, Vol. 107, No. 4, pp. 343-354, 2004.

상세보기
A. Tedgui, Z. Mallat, "Cytokines in atherosclerosis: pathogenic and regulatory pathways," Physiological Reviews, Vol. 86, No. 2, pp. 515-581, 2006.

상세보기
S. L. Freeman, W. K. MacNaughton, "Ionizing radiation induces iNOS-mediated epithelial dysfunction in the absence of an inflammatory response," American Journal of Physiology-Gastrointestinal and Liver Physiology, Vol. 278, No. 2, pp. G243-G250, 2000.

상세보기
F. Vannini, K. Kashfi, N. Nath, "The dual role of iNOS in cancer," Redox Biology, Vol. 6, No. 1, pp. 334-343, 2015.

상세보기
M. E. Kotas, M. J. Jurczak, C. Annicelli, M. P. Gillum, G. W. Cline, G. I. Shulman, R. Medzhitov, "Role of caspase-1 in regulation of triglyceride metabolism," Proceedings of the National Academy of Sciences of the United States of America, Vol. 110, No. 12, pp. 4810-4815, 2013.

상세보기
S. J. Son, K. J. Rhee, J. Lim, T. U. Kim, T. J. Kim, Y. S. Kim, "Triglyceride-induced macrophage cell death is triggered by caspase-1," Biological & pharmaceutical bulletin, Vol. 36, No. 1, pp. 108-113, 2013.

상세보기
A. Aronis, M. Aharoni-Simon, Z. Madar, O. Tirosh, "Triacylglycerol-induced impairment in mitochondrial biogenesis and function in J774.2 and mouse peritoneal macrophage foam cells," Archives of biochemistry and biophysics, Vol. 492, No. 1-2, pp. 74-81, 2009.

상세보기
A. Aronis, Z. Madar, O. Tirosh, "Lipotoxic effects of triacylglycerols in J774.2 macrophages," Nutrition, Vol. 24, No. 2, pp. 167-176, 2008.

상세보기
J. Lim, Y. S. Kim, S. H. Kim, Y. Cho, M. H. Lee, B. C. Jung, D. Jung, K. J. Rhee, "Triglyceride enhances susceptibility to TNF- ${\alpha}$ -induced cell death in THP-1 cells," Genes & Genomics, Vol. 36, No. 1, pp. 87-93, 2013.
J. B. Weinberg, M. A. Misukonis, P. J. Shami, S. N. Mason, D. L. Sauls, W. A. Dittman, E. R. Wood, G. K. Smith, B. McDonald, K. E. Bachus, A. F. Haney, D. L. Granger, "Human mononuclear phagocyte inducible nitric oxide synthase (iNOS): analysis of iNOS mRNA, iNOS protein, Biopterin, and nitric oxide production by blood monocytes and peritoneal macrophages," Blood, Vol. 86, No. 3, pp. 1184-1195, 1995.

상세보기
A. Aronis, Z. Madar, O. Tirosh, "Mechanism underlying oxidative stress-mediated lipotoxicity: exposure of J774.2 macrophages to triacylglycerols facilitates mitochondrial reactive oxygen species production and cellular necrosis," Free radical biology & medicine, Vol. 38, No. 9, pp. 1221-1230, 2005.

상세보기
P. Libby, P. M. Ridker, A. Maseri, "Inflammation and atherosclerosis," Circulation, Vol. 105, No. 9, pp. 1135-1143, 2002.

상세보기
A. K. Robertson, G. K. Hansson, "T cells in atherogenesis: for better or for worse?," Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 26, No. 11, pp. 2421-2432, 2006.

상세보기
Q. Wu, A. Allouch, I. Martins, N. Modjtahedi, E. Deutsch, J. L. Perfettini, "Macrophage biology plays a central role during ionizing radiation-elicited tumor response," Biomedical Journal, Vol. 40, No. 4, pp. 200-211, 2017.

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