افزایش سطح بیان ژن RAGE سودوموناس آئروژینوسا در افراد مبتلا به عفونت های خونی باکتریایی
محورهای موضوعی : باکتری شناسیفاطمه سادات حسینی 1 , اشرف کریمی نیک 2 , الهام نصیری 3
1 - گروه میکروبیولوژی.دانشکده علوم،دانشگاه آزاد اسلامی واحد کرمان،
2 - دانشگاه آزاد اسلامی واحد کرمان ، عضو هیات علمی
3 - گروه میکروبیولوژی، دانشکده علوم، دانشگاه آزاد اسلامی واحد کرمان، کرمان، ایران
کلید واژه: سودوموناس آئروژینوسا, عفونت خونی, RAGE, CXCL11,
چکیده مقاله :
سابقه و هدف: شناسایی باکتری های عامل عفونت خونی و تعامل آن با سیستم ایمنی،اهمیت بسیار زیادی دارد.RAGE نوعی گیرنده سلولی است که مولکول های با منشا درونی و خارجی را شناسایی می کند و CXC11 نیز درالقای پاسخ های ایمنی مناسب علیه میکروب ها شرکت می کند. هدف از این تحقیق،تعیین میزان سطح بیان این مولکول ها در بیماران با عفونت خونی و افراد سالم می باشد.مواد و روش ها: دراین مطالعه مورد-شاهدی، سطح بیان ژن RAGE و CXCL11 در 40 بیمار مبتلا به عفونت خونی و 40 فرد سالم به عنوان کنترل با استفاده از تکنیک Real time-PCRمورد بررسی قرار گرفت. تشخیص عفونت خونی با انجام کشت خون و بکارگیری آزمون های بیوشیمیایی باکتریایی انجام شد.یافته ها: سطح mRNA ژن RAGE در بیماران آلوده به سودوموناس آئروژینوسا در مقایسه با اشریشیا کلی ، استافیلوکوکوس اورئوس و اسینتوباکتر بامانی، به طور قابل توجهی افزایش داشت.اما سطح بیان CXCL11 در بین بیماران و گروه کنترل سالم افزایش معنی داری نداشت. همچنین در مقایسه باکتری های عامل عفونت ارتباط معنی داری مشاهده نگردید.نتیجه گیری: نتایج نشان داد که درعفونت خونی RAGE گیرنده مهمی در برابر سودوموناس آئروژینوسا می باشد. از این رو روش های کاهش میزان بیان مولکول هایRAGE ، می تواند نقش کاربردی در پاک سازی خون از این باکتری داشته باشد.
Background & Objectives: Identifying the bacteria causing the infection and interacting with the immune system is too essential. RAGE is a receptor, which recognizes several endogenous and exogenous molecules and CXCL11 participates in the induction of appropriate immune responses against microbes. The aim of the study was expression of the molecules in the patients suffering from septicemia versus healthy controls. Materials and Methods: In this case-control study, the expression levels of RAGE and CXCL11 in 40 patients with septicemia and 40 healthy subjects, were evaluated using Real time-PCR technique. Diagnosis of septicemia was performed by blood culture and bacterial biochemical tests. Results: RAGE mRNA levels were significantly increased in patients infected with Pseudomonas aeruginosa compared with Escherichia coli, Staphylococcus aureus and Acinetobacter bamanii. However, no significant increase in CXCL11 expression level was observed in patients and healthy controls and also in comparison with bacteria causing infection. Conclusion: Results showed that RAGE is a critical receptor against Pseudomonas aeruginosa during septicemia, Therefore, methods to reduce the expression of RAGE molecules can play a practical role in cleansing the blood from this bacterium.
Emerg Med. 2019; 2 (1):19.
2. Cirz RT, Chin JK, Andes DR, de Crécy-Lagard , Craig WA, Romesberg E. Inhibition of
mutation and combating the evolution of antibiotic resistance. PLoS Biol. 2005; 3(6): e1 6.
3. Robicsek A, Jacoby GA, Hooper DC. The worldwide emergence of plasmid-mediated
quinolone resistance. Lancet Infect Dis. 2006; 6(10):629–640.
4. Berit EE,Santini MP,Gielen J,Meembor S,Kronke M,Krut o.identification and characterization
of bacterial pathogens causing blood stream infections by DNA microarray .J Clin
Microbiol.2006 ;44( ):2389-239 .
5. Theresa AR, McKoy JM, Sepsis in Older Adults. Infect Dis Clin N Am. 201 ; 31: 731–742.
6. Bagheri , Askari A, Arababadi MK, Kennedy D. Can Toll-Like Receptor (TLR) 2 be
considered as a new target for immunotherapy against hepatitis B infection? Hum. Immunol.
2014; 5(6):549-54.
7. Karimi-Googheri M, Arababadi MK. TLR3 plays significant roles against hepatitis B virus.
Mol Biol Rep. 2014; 41(5):32 9-86.
8. Kang JH, Hwang SM, Chung I . S100A8, S100A9 and S100A12 activate airway epithelial
cells to produce MUC 5 AC via extracellular signal‐regulated kinase and nuclear factor‐ B
pathways. Immunol. 2015; 144(1): 9-90.
9. ranklin TC, Wohleb ES, Zhang , ogaça M, Hare B, Duman RS. Persistent increase in
microglial RAGE contributes to chronic stress–induced priming of depressive-like behavior.
Biol Psychiatry. 2018; 83(1):50-60.
10. Panezai J, Ghaffar A, Altamash M, Sundqvist K-G, Engström P-E, Larsson A. Correlation of
serum cytokines, chemokines, growth factors and enzymes with periodontal disease
parameters. PloS one. 201 ; 12(11): e0188945.
11. Erdel M, Laich A, Utermann G ,Werner E, Werner- elmayer G. The human gene encoding
SC B9B, a putative novel CXC chemokine, maps to human chromosome 4q21 like the
closely related genes for MIG (SC B9) and INP10 (SC B10). Cytogenet Genome Res.
1998; 81(3-4):2 1-2.
12. Ball JA , lisidou I, Blunt MD, Wood W, Ward SG. Hydrogen peroxide triggers a dual
signaling axis to selectively suppress activated human T lymphocyte migration. J. Immunol.
201 ; 198(9):36 9-89.
13. Kalil AC, Opal SM. Sepsis in the severely immunocompromised patient. Curr. Infect. Dis.
Rep. 2015; 1 (6):32.
14. Asadpour-Behzadi A, Kariminik A. RIG-1 and MDA5 are the important intracellular sensors
against bacteria in septicemia suffering patients. J. Appl. Biomed. 2018; 16(4):58-61.
15. orbes BA, Sahm D , Weissfeld AS. Diagnostic microbiology: Mosby St. Louis; 1998.
16. Afshari A. aghobi R. Karimi MH. Darbooie M. Azarpira N. 2014. Interleukin- 1 gene
expression and serum levels in acute rejected and non-rejected liver transplant patients. Iran J
Immunol .11:29-39.
17. Kariminik A, aghobi R, Dabiri S. CXCL9 expression and polyomavirus BK infectivity in
renal transplant patients with nephropathy. Cell Mol Biol. 2016; 62(1):104-8.
18. Kariminik A, aghobi R, Dabiri S. Association of BK irus Infection with CXCL11 gene
expression and protein levels in kidney transplant patients. Exp Clin Transplant. 2018; 16
(1):50-4.
19. Kariminik A, Dabiri S, aghobi R. Polyomavirus BK induces inflammation via up-regulation
of CXCL10 at translation levels in renal transplant patients with nephropathy. Inflammation.
2016; 39(4):1514-9.
20. Rezaeian A, aghobi R, Geramizadeh Increase in the level of MMP-2 gene expression in liver cirrhotic patients without chronic viral hepatitis B and C infections. J. Microbial
World .2019; 12(1):6-14.
21. Mohammadi Z, Momtaz H. Molecular typing of the Acinetobacter baumannii strains isolated
from blood infections using Multi Locus Sequence Typing (MLST). J. Microbial World.201 ;
10(2):104-113.
22. Denstaedt SJ, Singer BH, Standiford TJ. Sepsis and nosocomial infection: patient
characteristics, mechanisms, and modulation. ront Immunol. 2018; 23(9):2446.
23. Obritsch MD, ish DN, MacLaren R, Jung R. Nosocomial infections due to
multidrug‐resistant Pseudomonas aeruginosa: epidemiology and treatment options.
Pharmacotherapy. 2005; 25(10):1353-64.
24. Kariminik A, Baseri-Salehi M, Kheirkhah B. Pseudomonas aeruginosa quorum sensing
modulates immune responses: an updated review article. Immunol. Lett. 201 ; 190:1-6.
25. Schnurr M, Duewell P. Induction of immunogenic cell death by targeting RIG-I-like helicases
in pancreatic cancer. Oncoimmunol. 2014; 3(9): e95568 .
26. Selvaraj , Manne ND, Arvapalli R, Rice KM, Nandyala G, ankenhanel E, et al. Effect of
cerium oxide nanoparticles on sepsis induced mortality and N - B signaling in cultured
macrophages. Nanomedicine. 2015; 10(8):12 5-88.
27. Gao , ang Z, eng X , an TT, Jiang L, Guo R, et al. Interleukin-2 is elevated in
sepsis-induced myocardial dysfunction and mediates inflammation. Cytokine. 2016; 88:1-11.
28. Matsukura S, Kokubu , Kurokawa M, Kawaguchi M, Ieki K, Kuga H, et al. Role of RIG-I,
MDA-5, and PKR on the expression of inflammatory chemokines induced by synthetic
dsRNA in airway epithelial cells. Int. Arch. Allergy Immunol. 200 ; 143(1):80-3.
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Emerg Med. 2019; 2 (1):19.
2. Cirz RT, Chin JK, Andes DR, de Crécy-Lagard , Craig WA, Romesberg E. Inhibition of
mutation and combating the evolution of antibiotic resistance. PLoS Biol. 2005; 3(6): e1 6.
3. Robicsek A, Jacoby GA, Hooper DC. The worldwide emergence of plasmid-mediated
quinolone resistance. Lancet Infect Dis. 2006; 6(10):629–640.
4. Berit EE,Santini MP,Gielen J,Meembor S,Kronke M,Krut o.identification and characterization
of bacterial pathogens causing blood stream infections by DNA microarray .J Clin
Microbiol.2006 ;44( ):2389-239 .
5. Theresa AR, McKoy JM, Sepsis in Older Adults. Infect Dis Clin N Am. 201 ; 31: 731–742.
6. Bagheri , Askari A, Arababadi MK, Kennedy D. Can Toll-Like Receptor (TLR) 2 be
considered as a new target for immunotherapy against hepatitis B infection? Hum. Immunol.
2014; 5(6):549-54.
7. Karimi-Googheri M, Arababadi MK. TLR3 plays significant roles against hepatitis B virus.
Mol Biol Rep. 2014; 41(5):32 9-86.
8. Kang JH, Hwang SM, Chung I . S100A8, S100A9 and S100A12 activate airway epithelial
cells to produce MUC 5 AC via extracellular signal‐regulated kinase and nuclear factor‐ B
pathways. Immunol. 2015; 144(1): 9-90.
9. ranklin TC, Wohleb ES, Zhang , ogaça M, Hare B, Duman RS. Persistent increase in
microglial RAGE contributes to chronic stress–induced priming of depressive-like behavior.
Biol Psychiatry. 2018; 83(1):50-60.
10. Panezai J, Ghaffar A, Altamash M, Sundqvist K-G, Engström P-E, Larsson A. Correlation of
serum cytokines, chemokines, growth factors and enzymes with periodontal disease
parameters. PloS one. 201 ; 12(11): e0188945.
11. Erdel M, Laich A, Utermann G ,Werner E, Werner- elmayer G. The human gene encoding
SC B9B, a putative novel CXC chemokine, maps to human chromosome 4q21 like the
closely related genes for MIG (SC B9) and INP10 (SC B10). Cytogenet Genome Res.
1998; 81(3-4):2 1-2.
12. Ball JA , lisidou I, Blunt MD, Wood W, Ward SG. Hydrogen peroxide triggers a dual
signaling axis to selectively suppress activated human T lymphocyte migration. J. Immunol.
201 ; 198(9):36 9-89.
13. Kalil AC, Opal SM. Sepsis in the severely immunocompromised patient. Curr. Infect. Dis.
Rep. 2015; 1 (6):32.
14. Asadpour-Behzadi A, Kariminik A. RIG-1 and MDA5 are the important intracellular sensors
against bacteria in septicemia suffering patients. J. Appl. Biomed. 2018; 16(4):58-61.
15. orbes BA, Sahm D , Weissfeld AS. Diagnostic microbiology: Mosby St. Louis; 1998.
16. Afshari A. aghobi R. Karimi MH. Darbooie M. Azarpira N. 2014. Interleukin- 1 gene
expression and serum levels in acute rejected and non-rejected liver transplant patients. Iran J
Immunol .11:29-39.
17. Kariminik A, aghobi R, Dabiri S. CXCL9 expression and polyomavirus BK infectivity in
renal transplant patients with nephropathy. Cell Mol Biol. 2016; 62(1):104-8.
18. Kariminik A, aghobi R, Dabiri S. Association of BK irus Infection with CXCL11 gene
expression and protein levels in kidney transplant patients. Exp Clin Transplant. 2018; 16
(1):50-4.
19. Kariminik A, Dabiri S, aghobi R. Polyomavirus BK induces inflammation via up-regulation
of CXCL10 at translation levels in renal transplant patients with nephropathy. Inflammation.
2016; 39(4):1514-9.
20. Rezaeian A, aghobi R, Geramizadeh Increase in the level of MMP-2 gene expression in liver cirrhotic patients without chronic viral hepatitis B and C infections. J. Microbial
World .2019; 12(1):6-14.
21. Mohammadi Z, Momtaz H. Molecular typing of the Acinetobacter baumannii strains isolated
from blood infections using Multi Locus Sequence Typing (MLST). J. Microbial World.201 ;
10(2):104-113.
22. Denstaedt SJ, Singer BH, Standiford TJ. Sepsis and nosocomial infection: patient
characteristics, mechanisms, and modulation. ront Immunol. 2018; 23(9):2446.
23. Obritsch MD, ish DN, MacLaren R, Jung R. Nosocomial infections due to
multidrug‐resistant Pseudomonas aeruginosa: epidemiology and treatment options.
Pharmacotherapy. 2005; 25(10):1353-64.
24. Kariminik A, Baseri-Salehi M, Kheirkhah B. Pseudomonas aeruginosa quorum sensing
modulates immune responses: an updated review article. Immunol. Lett. 201 ; 190:1-6.
25. Schnurr M, Duewell P. Induction of immunogenic cell death by targeting RIG-I-like helicases
in pancreatic cancer. Oncoimmunol. 2014; 3(9): e95568 .
26. Selvaraj , Manne ND, Arvapalli R, Rice KM, Nandyala G, ankenhanel E, et al. Effect of
cerium oxide nanoparticles on sepsis induced mortality and N - B signaling in cultured
macrophages. Nanomedicine. 2015; 10(8):12 5-88.
27. Gao , ang Z, eng X , an TT, Jiang L, Guo R, et al. Interleukin-2 is elevated in
sepsis-induced myocardial dysfunction and mediates inflammation. Cytokine. 2016; 88:1-11.
28. Matsukura S, Kokubu , Kurokawa M, Kawaguchi M, Ieki K, Kuga H, et al. Role of RIG-I,
MDA-5, and PKR on the expression of inflammatory chemokines induced by synthetic
dsRNA in airway epithelial cells. Int. Arch. Allergy Immunol. 200 ; 143(1):80-3.