NEUROIMMUNOENDOCRINE PROFILE OF SARCOID GRANULEMA: EXPRESSION OF SIGNAL MOLECULES

DOI: https://doi.org/10.29296/24999490-2020-01-03

P.K. Yablonsky(1), V.O. Polyakova(1, 2), Yu.S. Krylova(1, 4), A.O. Drobintseva(1, 3), D.O. Leonteva1, E.G. Sokolovich(1), I.M. Kvetnoy(1, 2) 1-Saint-Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Healthcare of the Russian Federation, Ligovskij avenue, 2–4, Saint-Petersburg, 191036, Russian Federation; 2-Saint-Petersburg University, Universitetskaya Embankment, 7–9, Saint-Petersburg, 199034, Russian Federation; 3-St. Petersburg State Pediatric Medical University, Litovskaya street, 2, Saint-Petersburg, 194100, Russian Federation; 4-Pavlov First Saint Petersburg State Medical University, Street L’va Tolstogo, 6–8, Saint-Petersburg, 197022, Russian Federation E-mail: [email protected]

Introduction. Sarcoidosis is a systemic granulomatous disease of unknown etiology, which leads to disruption of the human respiratory system and can lead to damage to other systems. In clinical practice, doctors often run into difficulties in differentiating sarcoidosis from tuberculosis – another granulomatous disease, because of their similar clinical and radiological pictures. None of the existing methods for diagnosing sarcoidosis or tuberculosis is absolute. However, the correct and timely diagnosis plays an important role in the successful treatment of these pulmonary pathologies. The aim of the study. Determination of the neuro-immuno-endocrine profile of sarcoid granuloma. Methods. Namely, proteins were studied: interleukin-8 (IL8), Protein gene product 9.5 (PGP9.5), tissue inhibitor of metalloproteinases (TIMP1), melatonin receptor 1A (RM-1A), melatonin receptor 1B (RM-1B). Results. Studies have shown sarcoid granulomas to express IL-8 with the presence of nerve – PGP9.5 positive terminals in peri-granuloma tissue, thus labeling granuloma, we suggest IL-8 be able to become a diagnostic marker of lung sarcoidosis. The data on the expression of TIMP1, RM-1A, and RM-2B are ambiguous and require further study. Conclusion. Thus, the neuro-immuno-endocrine aspects of granulomatous inflammation are interesting for further research at various stages of sarcoidosis, as well as for tuberculosis.
Keywords: 
рulmonary sarcoidosis, granulomatous inflammation, sarcoid granuloma, IL-8, neuroimmunoendocrine interactions
Список литературы: 
  1. Kunkel S., Standiford Th., Kasahara K., Strieter R. Interleukin-8 (IL-8): The Major Neutrophil Chemotactic Factor in the Lung. Experimental Lung Research. 1991; 17: 17–23. https://doi.org/10.3109/01902149109063278
  2. Hoffmann E., Dittrich–Breiholz O., Holtmann H., Kracht M. Multiple control of interleukin-8 gene expression. J. of leukocyte biology. 2002; 5 (72): 847–55. https://doi.org/10.1189/jlb.72.5.847
  3. Mortaz E., Sereshki H.A., Abedini A., Kiani A., Mirsaeidi M., Soroush D., Garssen J., Velayati A., Redegeld F., Adcock I. Association of serum TNF-α, IL-8 and free light chain with HLA-DR B alleles expression in pulmonary and extra-pulmonary sarcoidosis. J. of Inflammation. 2015; 12: 21. https://doi.org/10.1186/s12950-015-0066-3
  4. Day I., Hinks L., Thompson R. The structure of the human gene encoding protein gene product 9.5 (PGP9.5), a neuron-specific ubiquitin C-terminal hydrolase. Biochemical J. 1990; 268 (2): 521–4. https://doi.org/10.1042/bj2680521
  5. Nishida M., Namiki T., Sone Y., Hashimoto T., Tokoro S., Hanafusa T., Yokozeki H. Acquired anhidrosis associated with systemic sarcoidosis: quantification of nerve fibers around eccrine glands by confocal microscopy. British J. of Dermatology. 2017; 1 (178). https://doi.org/10.1111/bjd.15880
  6. Raeeszadeh-Sarmazdeh M., Sankaran B., Radisky D., Radisky E. Engineering Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) as a Selective Inhibitor of Matrix Metalloproteinase-3 (MMP-3) for Therapeutic Targeting. The FASEB J. 2018; 32 (1): 798–7.
  7. Jiang D., Huang X., Geng J., Dong R., Li Sh., Liu Zh., Wang Ch., Dai H. Pulmonary fibrosis in a mouse model of sarcoid granulomatosis induced by booster challenge with Propionibacterium acnes. Oncotarget. 2016; 7 (23): 33703–14. https://doi.org/10.18632/oncotarget.9397
  8. Selman M., Ruiz V., Cabrera S., Segura L., Ramirez R, Barrios R., Pardo A. TIMP-1, -2, -3, and -4 in idiopathic pulmonary fibrosis. A prevailing nondegradative lung microenvironment? Am. J. of Physiology-Lung Cellular and Molecular Physiology. 2000; 279 (3): 562–74. https://doi.org/10.1152/ajplung.2000.279.3.L562
  9. Bespjatyh A.Ju., Brodskij V.Ja., Burlakova O.V., Golichenkov V.A., Voznesenskaja L.A., Kolesnikov D.B., Molchanov A.Ju., Rappoport S.I. Melatonin: teorija i praktika. M.: MEDPRAKTIKA-M, 2009. [Bespyatyx A.Yu., Brodskij V.Ya., Burlakova O.V., Golichenkov V.A., Voznesenskaya L.A., Kolesnikov D.B., Molchanov A.Yu., Rappoport S.I. Melatonin: theory and practice. M.: MEDPRAKTIKA-M, 2009 (in Russian)]
  10. Jarmolinskaja M.I., Zajtsev D.V., Thazaplizheva S.Sh. Melatonin i genital'nyj endometrioz – novye vozmozhnosti terapii. Zhurnal akusherstva i zhenskih boleznej. 2015; 1 (64): 67–70. [Yarmolinskaya M.I., Zajcev D.V., Txazaplizheva S.Sh. Melatonin and genital endometriosis – new treatment options. Zhurnal akusherstva i zhenskix boleznej. 2015; 1 (64): 67–70 (in Russian)]
  11. Sychevskaja K.A., Erohina M.V., Lepeha L.N. Metod komp'juternoj morfometrii dlja differentsial'noj diagnostiki nekrotizirujuschego sarkoidnogo granulematoza i tuberkuleza. Klinicheskaja i eksperimental'naja morfologija. 2017; 1: 59–64. [Sychevskaya K.A., Eroxina M.V., Lepexa L.N. Method of computer morphometry for the differential diagnosis of necrotizing sarcoid granulomatosis and tuberculosis. Klinicheskaya i e’ksperimental’naya morfologiya. 2017; 1: 59–64 (in Russian)]
  12. Yadegari M., Harijani Sh.M., Hamidiyan Gh., Ebrahimi M. Effects of high-intensity interval training on chronic inflammation of lung tissue in healthy rats. Biomedical and health. 2017; 2 (3): 137–49. https://doi.org/10.30468/JBIOM.2017.55917
  13. Broos C. E., van Nimwegen M., Hoogsteden H. C., Hendriks R. W., Kool M., van den Blink, B. Granuloma formation in pulmonary sarcoidosis. Frontiers in immunology. 2013; 4: 437. https://doi.org/10.3389/fimmu.2013.00437