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Ulinastatin suppresses lipopolysaccharide-induced prostaglandin E2 synthesis and nitric oxide production through the downregulation of nuclear factorκB in BV2 mouse microglial cells

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Ulinastatin is an intrinsic serine-protease urinary trypsin inhibitor that can be extracted and purified from human urine. Urinary trypsin inhibitors are widely used to treat patients with acute inflammatory disorders, such as shock and pancreatitis. However, although the anti-inflammatory activities of urinary trypsin inhibitors have been investigated, the mechanisms underlying their actions are not yet fully understood. In the present study, we evaluated the effect of ulinastatin on lipopolysaccharide (LPS)-induced inflammation in relation with nuclear factor-κB (NF-κB) activation using BV2 mouse microglial cells. To accomplish this, we performed a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, reverse transcription-polymerase chain reaction (RT-PCR), western blot analysis, electrophoretic mobility gel shift assay (EMSA), prostaglandin E2 (PGE2) immunoassay and nitric oxide (NO) detection. The results demonstrated that ulinastatin suppressed PGE2 synthesis and NO production by inhibiting the LPS-induced mRNA and protein expression of cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS) in BV2 mouse microglial cells. Ulinastatin suppressed the activation of NF-κB in the nucleus. These findings demonstrate that ulinastatin exerts analgesic and anti-inflammatory effects that possibly occur via the suppression of COX-2 and iNOS expression through the downregulation of NF-κB activity.
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Document Type: Research Article

Affiliations: 1: Department of Physical Therapy, Kyungnam University, Changwon 631-701, Republic of Korea 2: Department of Physiology, Kyung Hee University College of Medicine, Seoul 130-701, Republic of Korea 3: Department of Microbiology, Kyung Hee University College of Medicine, Seoul 130-701, Republic of Korea 4: Department of Pediatrics, Eulji General Hospital, Eulji University School of Medicine, Seoul 139-872, Republic of Korea 5: Department of Anesthesiology and Pain Medicine, Kang Dong Kyung Hee Hospital, Kyung Hee University College of Medicine, Seoul 134-890, Republic of Korea

Publication date: January 1, 2013

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  • The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.

    The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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