We investigated the effect of a Multiwave Locked System laser (with a simultaneous 808 nm continuous emission and 905 nm pulse emission) on the spinal cord after spinal cord injury (SCI) in rats. The functional recovery was measured by locomotor tests (BBB, Beam walking, MotoRater) and a sensitivity test (Plantar test). The locomotor tests showed a significant improvement of the locomotor functions of the rats after laser treatment from the first week following lesioning, compared to the controls. The laser treatment significantly diminished thermal hyperalgesia after SCI as measured by the Plantar test. The atrophy of the soleus muscle was reduced in the laser treated rats. The histopathological investigation showed a positive effect of the laser therapy on white and gray matter sparing. Our data suggests an upregulation of M2 macrophages in laser treated animals by the increasing number of double labeled CD68+/CD206+ cells in the cranial and central parts of the lesion, compared to the control animals. A shift in microglial/macrophage polarization was confirmed by gene expression analysis by significant mRNA downregulation of Cd86 (marker of inflammatory M1), and non-significant upregulation of Arg1 (marker of M2). These results demonstrated that the combination of 808 nm and 905 nm wavelength light is a promising non-invasive therapy for improving functional recovery and tissue sparing after SCI.
- MeSH
- antigeny CD86 genetika metabolismus MeSH
- antigeny diferenciační myelomonocytární genetika metabolismus MeSH
- CD antigeny genetika metabolismus MeSH
- krysa rodu rattus MeSH
- laserová terapie s nízkou intenzitou světla metody MeSH
- lektiny typu C genetika metabolismus MeSH
- lektiny vázající mannosu genetika metabolismus MeSH
- lokomoce MeSH
- mícha metabolismus patologie MeSH
- poranění míchy terapie MeSH
- potkani Wistar MeSH
- receptory buněčného povrchu genetika metabolismus MeSH
- regenerace míchy MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Treatment of murine EL4 T cell lymphoma with N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer conjugates of doxorubicin (Dox) leads to complete tumor regression and to the development of therapy-dependent longlasting cancer resistance. This phenomenon occurs with two types of Dox conjugates tested, despite differences in the covalent linkage of Dox to the polymer carrier. Such a cancer resistance cannot fully express in conventional treatment with free Dox, due to substantial immunotoxicity of the treatment, which was not observed in the polymer conjugates. In this study, calreticulin (CRT) translocation and high mobility group box-1 protein (HMGB1) release was observed in EL4 cells treated with a conjugate releasing Dox by a pH-dependent manner. As a result, the treated tumor cells were engulfed by dendritic cells (DC) in vitro, and induced their expression of CD80, CD86, and MHC II maturation markers. Conjugates with Dox bound via an amide bond only increased translocation of HSPs to the membrane, which led to an elevated phagocytosis but was not sufficient to induce increase of the maturation markers on DCs in vitro. Both types of conjugates induced engulfment of the target tumor cells in vivo, that was more intense than that seen with free Dox. It means that the induction of anti-tumor immunity documented upon treatment of EL4 lymphoma with HPMA-bound Dox conjugates does not rely solely on CRT-mediated cell death, but involves multiple mechanisms.
- MeSH
- antigeny CD80 metabolismus MeSH
- antigeny CD86 metabolismus MeSH
- antitumorózní látky aplikace a dávkování chemie toxicita MeSH
- apoptóza účinky léků MeSH
- chemorezistence účinky léků MeSH
- dendritické buňky cytologie imunologie MeSH
- doxorubicin aplikace a dávkování analogy a deriváty chemie toxicita MeSH
- fagocytóza MeSH
- kalretikulin metabolismus MeSH
- koncentrace vodíkových iontů MeSH
- kyseliny polymethakrylové aplikace a dávkování chemie toxicita MeSH
- lymfom T-buněčný farmakoterapie imunologie MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nosiče léků chemie MeSH
- protein HMGB1 metabolismus MeSH
- proteiny tepelného šoku metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
To elucidate the role of innate immune responses in celiac disease, we investigated the effect of gliadin on blood monocytes from patients with celiac disease. Gliadin induced substantial TNF-alpha and IL-8 production by monocytes from patients with active celiac disease, lower levels by monocytes from patients with inactive celiac disease, and even lower levels by monocytes from healthy donors. In healthy donor monocytes gliadin induced IL-8 from monocytes expressing HLA-DQ2 and increased monocyte expression of the costimulatory molecules CD80 and CD86, the dendritic cell marker CD83, and the activation marker CD40. Gliadin also increased DNA binding activity of NF-kappaB p50 and p65 subunits in monocytes from celiac patients, and NF-kappaB inhibitors reduced both DNA binding activity and cytokine production. Thus, gliadin activation of HLA-DQ2(+) monocytes leading to chemokine and proinflammatory cytokine production may contribute to the host innate immune response in celiac disease.
- MeSH
- aktivace makrofágů imunologie MeSH
- antigeny CD40 metabolismus MeSH
- antigeny CD80 metabolismus MeSH
- antigeny CD86 metabolismus MeSH
- CD antigeny metabolismus MeSH
- celiakie imunologie metabolismus MeSH
- cytokiny biosyntéza MeSH
- financování organizované MeSH
- gliadin metabolismus MeSH
- HLA-DQ antigeny metabolismus MeSH
- imunoglobuliny metabolismus MeSH
- interleukin-8 biosyntéza MeSH
- lidé MeSH
- membránové glykoproteiny metabolismus MeSH
- monocyty metabolismus MeSH
- NF-kappa B metabolismus MeSH
- peptidové fragmenty MeSH
- průtoková cytometrie MeSH
- TNF-alfa biosyntéza MeSH
- Check Tag
- lidé MeSH
