Modulation of IL-6 receptor/STAT3 downstream signaling in rheumatoid arthritis patients.

Interleukin-6 (IL-6) is a relevant cytokine in rheumatoid arthritis (RA) pathogenesis, potentially activating Janus kinases (JAK)-1, -2, and tyrosine kinase 2 (TYK2), and thus, three signal transducer and activator of transcription (STAT)-1, -3 or - 5 pathways. This pilot study aims to explore differences in phosphorylated (p)STAT3 levels among patients with RA, those not classified as RA (nRA), and healthy donors (HD), providing some clues on the relative contribution of each JAK protein to the downstream of the IL-6-induced STAT3 pathway. Clinical data and blood samples from 80 subjects (41 RA, 14 nRA, and 25 HD) were collected.

Anti-aquaporin-5 and anti-poly-U-binding-factor-60kDa protein antibodies in primary Sjögren's disease patients: preliminary data and correlation with disease activity indices.

Objectives: In primary Sjögren's disease (pSjD), in addition to glandular inflammation and atrophy, functional secretion impairment may contribute to dryness. Altered protein distribution and antibodies against aquaporin-5 (anti-AQP5) and poly-U-binding factor 60kDa protein (anti-PUF60) have been reported in pSjD and may be specifically implicated in the glandular secretive processes. This study aimed to assess the occurrence of serum anti-AQP5 and anti-PUF60 antibodies and their correlations with clinical and laboratory features of pSjD.

Body mass index and adipokines/cytokines dysregulation in systemic sclerosis.

Body fat has regulatory functions through producing cytokines and adipokines whose role in the pathogenesis of systemic sclerosis (SSc) is currently emerging. Changes in body mass, either over- or underweight, entail a dysregulation of the cytokine/adipokine network that may impact upon SSc disease activity. We evaluated serum levels of adipokines and cytokines in SSc patients and correlated them to clinical features and body mass index (BMI) categories.

Serum sCD40L levels are increased in patients with psoriatic arthritis and are associated with clinical response to apremilast.

The pathogenesis of psoriatic arthritis (PsA) involves several pathways, including the CD40/CD40L signaling which promotes the release of multiple cytokines. Transmembrane CD40L is also released in soluble form (sCD40L) and phosphodiesterase 4 (PDE4) seems to be involved in its cleavage. We aimed to investigate whether apremilast, a PDE4 inhibitor, could modify circulating levels of sCD40L in PsA patients, and the possible associations of these changes with clinical response.

Possible role of adipocytokines in systemic sclerosis-associated small pericardial effusion.

Introduction: Pericardial effusion is a common manifestation of systemic sclerosis, but its pathogenesis has been poorly investigated. Adipokines and interleukins may play a role in the pathophysiology of pericardial effusion. This study aimed at evaluating serum levels of adipokines and interleukins in systemic sclerosis patients with and without pericardial effusion.

Correlation between serum levels of IL-15 and IL-17 in patients with idiopathic inflammatory myopathies.

Objectives: To assess the serum levels of interleukin (IL)-15 and IL-17 in patients with idiopathic inflammatory myopathies (IIM) and correlate them with levels of IL-1 receptor antagonist (IL-1ra), IL-6, IL-10, interferon (IFN)-γ, monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1α, and MIP-1β. Possible correlations with disease activity parameters were also evaluated.

Method: Sera from 14 patients with new-onset polymyositis (PM), 10 with dermatomyositis (DM), seven with anti-synthetase syndrome (ASS) and 19 healthy controls (HC) were analysed by multiplex immunoassay.

Possible interplay between interleukin-15 and interleukin-17 into the pathogenesis of idiopathic inflammatory myopathies.

The aim of this study was to assess the serum levels of interleukin (IL)-15 and IL-17 in patients with idiopathic inflammatory myopathies (IIM) and correlate them with IL-6, IL-10, monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), MIP-1β levels. Possible correlations with disease activity parameters were also evaluated. Sera from 14 polymyositis (PM), 10 dermatomyositis (DM), 7 anti-synthetase syndrome new onset patients and 19 healthy controls (HCs) were analyzed by multiplex immunoassay.

The mitochondrial oxoglutarate carrier: cysteine-scanning mutagenesis of transmembrane domain IV and sensitivity of Cys mutants to sulfhydryl reagents.

Using a functional mitochondrial oxoglutarate carrier mutant devoid of Cys residues (C-less carrier), each amino acid residue in transmembrane domain IV and flanking hydrophilic loops (from T179 to S205) was replaced individually with Cys. The great majority of the 27 mutants exhibited significant oxoglutarate transport in reconstituted liposomes as compared to the activity of the C-less carrier. In contrast, Cys substitution for G183, R190, Q198, and Y202, in either C-less or wild-type carriers, yielded molecules with complete loss of oxoglutarate transport activity.

Inactivation of the reconstituted oxoglutarate carrier from bovine heart mitochondria by pyridoxal 5'-phosphate.

The effect of pyridoxal 5'-phosphate and some other lysine reagents on the purified, reconstituted mitochondrial oxoglutarate transport protein has been investigated. The inhibition of oxoglutarate/oxoglutarate exchange by pyridoxal 5'-phosphate can be reversed by passing the proteoliposomes through a Sephadex column but the reduction of the Schiff's base by sodium borohydride yielded an irreversible inactivation of the oxoglutarate carrier protein. Pyridoxal 5'-phosphate, which caused a time- and concentration-dependent inactivation of oxoglutarate transport with an IC50 of 0.

Inhibition of the reconstituted mitochondrial oxoglutarate carrier by arginine-specific reagents.

The effect of arginine-specific reagents on the function of the purified and reconstituted oxoglutarate carrier protein of the inner mitochondrial membrane has been investigated. The alpha-dicarbonyl reagents 2,3-butanedione, 2,3-pentanedione, 2,3- and 3,4-hexanedione, 1-phenyl-1,2-propanedione, phenylglyoxal, and phenylglyoxal derivatives caused a concentration-dependent inhibition of oxoglutarate transport with an IC50 of 0.05 mM for 2,3-hexanedione, 0.

Photoaffinity labeling of the mitochondrial oxoglutarate carrier by azido-phthalonate.

The effect of azido-phthalonate, a photoreactive analogue of oxoglutarate, on the transport of oxoglutarate was investigated in proteoliposomes reconstituted with the purified oxoglutarate carrier. In the dark, azido-phthalonate inhibits the reconstituted oxoglutarate/oxoglutarate exchange in a competitive manner with a Ki of 0.38 mM.

myo-inositol transport in rat intestinal brush border membrane vesicles, and its inhibition by D-glucose.

The uptake of myo-inositol into rat intestinal brush border membrane vesicles (BBMV) has been investigated. It is demonstrated that myo-inositol is transported into the vesicles by a secondary active process, specifically using the sodium gradient as the driving force. In the absence of sodium gradient, the transport reaction is still sodium dependent, and rheogenic, indicating that a myo-inositol/sodium cotransport is likely to occur.