Multiple sclerosis (MS) is an autoimmune neurodegenerative disease characterized by chronic brain inflammation. Leukocyte infiltration of brain tissue causes inflammation, demyelination, and the subsequent formation of sclerotic plaques, which are a hallmark of MS. Activation of proinflammatory cytokines is essential for regulation of lymphocyte migration across the blood–brain barrier. We demonstrate increased levels of many cytokines, including IL-2RA, CCL5, CCL11, MIF, CXCL1, CXCL10, IFNγ, SCF, and TRAIL, were upregulated in cerebrospinal fluid (CSF), whereas IL-17, CCL2, CCL3, CCL4, and IL-12(p40) were activated in MS serum. Interaction analysis of cytokines in CSF demonstrated a connection between IFNγ and CCL5 as well as MIF. Many cells can contribute to production of these cytokines including CD8 and Th1 lymphocytes and astrocytes. Therefore, we suggest that IFNγ released by Th1 lymphocytes can activate astrocytes, which then produce chemoattractants, including CCL5 and MIF. These chemokines promote an inflammatory milieu and interact with multiple chemokines including CCL27 and CXCL1. Of special note, upregulation of CCL27 was found in CSF of MS cases. This observation is the first to demonstrate CCL27 as a potential contributor of brain pathology in MS. Our data suggest that CCL27 may be involved in activation and migration of autoreactive encephalitogenic immune effectors in the brain. Further, our data support the role of Th1 lymphocytes in the pathogenesis of brain inflammation in MS, with several cytokines playing a central role.

The cytochalasin B-induced membrane vesicles (CIMVs) are suggested to be used as a vehicle for the delivery of therapeutics. However, the angiogenic activity and therapeutic potential of human mesenchymal stem/stromal cells (MSCs) derived CIMVs (CIMVs-MSCs) remains unknown. Objectives: The objectives of this study were to analyze the morphology, size distribution, molecular composition, and angiogenic properties of CIMVs-MSCs. Methods: The morphology of CIMVs-MSC was analyzed by scanning electron microscopy. The proteomic analysis, multiplex analysis, and immunostaining were used to characterize the molecular composition of the CIMVs-MSCs. The transfer of surface proteins from a donor to a recipient cell mediated by CIMVs-MSCs was demonstrated using immunostaining and confocal microscopy. The angiogenic potential of CIMVs-MSCs was evaluated using an in vivo approach of subcutaneous implantation of CIMVs-MSCs in mixture with Matrigel matrix. Results: Human CIMVs-MSCs retain parental MSCs content, such as growth factors, cytokines, and chemokines: EGF, FGF-2, Eotaxin, TGF-α, G-CSF, Flt-3L, GM-CSF, Fractalkine, IFNα2, IFN-γ, GRO, IL-10, MCP-3, IL-12p40, MDC, IL-12p70, IL-15, sCD40L, IL-17A, IL-1RA, IL-1a, IL-9, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IP-10, MCP-1, MIP_1a, MIP-1b, TNF-α, TNF-β, VEGF. CIMVs-MSCs also have the expression of surface receptors similar to those in parental human MSCs (CD90+, CD29+, CD44+, CD73+). Additionally, CIMVs-MSCs could transfer membrane receptors to the surfaces of target cells in vitro. Finally, CIMVs-MSCs can induce angiogenesis in vivo after subcutaneous injection into adult rats. Conclusions: Human CIMVs-MSCs have similar content, immunophenotype, and angiogenic activity to those of the parental MSCs. Therefore, we believe that human CIMVs-MSCs could be used for cell free therapy of degenerative diseases.

Inflammasomes are cytosolic polyprotein complexes formed in response to various external and internal stimuli, including viral and bacterial antigens. The main product of the inflammasome is active caspase 1 which proteolytically cleaves, releasing functional interleukin-1 beta (IL-1β) and interleukin-18 (IL-18). These cytokines play a central role in shaping immune response to pathogens. In this review, we will focus on the mechanisms of inflammasome activation, as well as their role in development of Th1, Th2, and Th17 lymphocytes. The contribution of cytokines IL-1β, IL-18, and IL-33, products of activated inflammasomes, are summarized. Additionally, the role of cytokines released from tissue cells in promoting differentiation of lymphocyte populations is discussed.

The first representative of metal complexes containing two different polyhedral clusters (namely, a fullerene and a carborane) as ligands in the same coordination sphere of the metal atom, [(η 2 -C 60 )Ir(o-HCB 10 H 9 CCH 2 PPh 2 -B,P)(tBuNC) 2 ] (II), was synthesized in the reaction of C 60 with the metallacyclic carboranyliridium dihydride complex [Ir(H) 2 (o-HCB 10 H 9 CCH 2 PPh 2 -B,P)(PPh 3 )(L)] (L = CO or PPh 3 ) by reflux in toluene in the presence of 2 equiv. of tBuNC. The compound obtained was characterized by analytical and spectro-

The interaction of C60 fullerene with the cis‐dihydride osmium complex [OsH2(CO)(PPh3)3] (I) in the presence of tBuNC gives a novel metal complex [(η2‐C60)Os(CO)‐(tBuNC)(PPh3)2] (II) as the first mononuclear osmium complex with an η2‐coordinated fullerene ligand. Complex II was isolated and characterized by elemental analysis, UV, IR, 1H and 31P NMR spectroscopy. An X‐ray diffraction study of II as its dichlorobenzene solvate revealed a distorted trigonal bipyramidal coordination of the Os atom, with a 6/6 bond of C60 and two PPh3 ligands in the equatorial plane and CO and tBuNC as axial ligands. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)