| 000 | 04035nlm1a2200481 4500 | ||
|---|---|---|---|
| 001 | 663386 | ||
| 005 | 20231030041852.0 | ||
| 035 | _a(RuTPU)RU\TPU\network\34555 | ||
| 035 | _aRU\TPU\network\28422 | ||
| 090 | _a663386 | ||
| 100 | _a20210209a2020 k y0engy50 ba | ||
| 101 | 0 | _aeng | |
| 102 | _aCH | ||
| 135 | _adrcn ---uucaa | ||
| 181 | 0 | _ai | |
| 182 | 0 | _ab | |
| 200 | 1 |
_aTherapeutic Effects of Tryptanthrin and Tryptanthrin-6-Oxime in Models of Rheumatoid Arthritis _fL. N. Kirpotina, I. A. Schepetkin (Shchepyotkin), D. R. Hammaker [et al.] |
|
| 203 |
_aText _celectronic |
||
| 300 | _aTitle screen | ||
| 330 | _aRheumatoid arthritis (RA) is a chronic autoimmune disease involving joint and bone damage that is mediated in part by proteases and cytokines produced by synovial macrophages and fibroblast-like synoviocytes (FLS). Although current biological therapeutic strategies for RA have been effective in many cases, new classes of therapeutics are needed. We investigated anti-inflammatory properties of the natural alkaloid tryptanthrin (TRYP) and its synthetic derivative tryptanthrin-6-oxime (TRYP-Ox). Both TRYP and TRYP-Ox inhibited matrix metalloproteinase (MMP)-3 gene expression in interleukin (IL)-1β-stimulated primary human FLS, as well as IL-1β-induced secretion of MMP-1/3 by FLS and synovial SW982 cells and IL-6 by FLS, SW982 cells, human umbilical vein endothelial cells (HUVECs), and monocytic THP-1 cells, although TRYP-Ox was generally more effective and had no cytotoxicity in vitro. Evaluation of the therapeutic potential of TRYP and TRYP-Ox in vivo in murine arthritis models showed that both compounds significantly attenuated the development of collagen-induced arthritis (CIA) and collagen-antibody-induced arthritis (CAIA), with comparable efficacy. Collagen II (CII)-specific antibody levels were similarly reduced in TRYP- and TRYP-Ox-treated CIA mice. TRYP and TRYP-Ox also suppressed proinflammatory cytokine production by lymph node cells from CIA mice, with TRYP-Ox being more effective in inhibiting IL-17A, granulocyte-macrophage colony-stimulating factor (GM-CSF), and receptor activator of nuclear factor-κB ligand (RANKL). Thus, even though TRYP-Ox generally had a better in vitro profile, possibly due to its ability to inhibit c-Jun N-terminal kinase (JNK), both TRYP and TRYP-Ox were equally effective in inhibiting the clinical symptoms and damage associated with RA. Overall, TRYP and/or TRYP-Ox may represent potential new directions for the pursuit of novel treatments for RA. | ||
| 461 | _tFrontiers in Pharmacology | ||
| 463 |
_tVol. 11 _v[1145, 17 p.] _d2020 |
||
| 610 | 1 | _aэлектронный ресурс | |
| 610 | 1 | _aтруды учёных ТПУ | |
| 610 | 1 | _ac-Jun N-terminal kinase | |
| 610 | 1 | _atryptanthrin | |
| 610 | 1 | _atryptanthrin-6-oxime | |
| 610 | 1 | _akinase inhibitor | |
| 610 | 1 | _aarthritis | |
| 610 | 1 | _ainflammation | |
| 610 | 1 | _acollagen-induced arthritis | |
| 610 | 1 | _acollagen antibody-induced arthritis | |
| 610 | 1 | _aингибиторы | |
| 701 | 1 |
_aKirpotina _bL. N. _gLiliya Nikolaevna |
|
| 701 | 1 |
_aSchepetkin (Shchepyotkin) _bI. A. _cdoctor-biophysicist _cleading researcher of Tomsk Polytechnic University, candidate of medical science _f1962- _gIgor Aleksandrovich _2stltpush _3(RuTPU)RU\TPU\pers\37358 |
|
| 701 | 1 |
_aHammaker _bD. R. _gDeepa |
|
| 701 | 1 |
_aKuhs _bA. _gAmanda |
|
| 701 | 1 |
_aKhlebnikov _bA. I. _cChemist _cProfessor of Tomsk Polytechnic University _f1963- _gAndrey Ivanovich _2stltpush _3(RuTPU)RU\TPU\pers\33927 |
|
| 701 | 1 |
_aQuinn _bM. T. _gMark |
|
| 712 | 0 | 2 |
_aНациональный исследовательский Томский политехнический университет _bИнженерная школа новых производственных технологий _bНаучно-образовательный центр Н. М. Кижнера _h7872 _2stltpush _3(RuTPU)RU\TPU\col\23556 |
| 801 | 2 |
_aRU _b63413507 _c20210209 _gRCR |
|
| 856 | 4 | _uhttps://doi.org/10.3389/fphar.2020.01145 | |
| 942 | _cCF | ||