chondroitin-sulfates and Psoriasis

To evaluate the immune-modulator effect of chondroitin sulfate (CS) by means of the review of the literature.. Inflammatory reactions are primarily originated by infectious agents, immune reactions and by sterile tissue lesions that activate membrane receptors by means of pathogen-associated molecular patterns, tissue breakdown products and cytokines. The activation of membrane receptors triggers the phosphorylation of mitogen activated protein kinases and of the nuclear factor kappaB (NF-kappaB). The binding of NF-kappaB to the promoter of target genes enhances the expression of pro-inflammatory cytokines, inducible nitric oxide synthase, cyclooxygenase 2, phospholipase A2, and matrix metalloproteases, proteins that contribute to tissue damage and to the inflammatory reaction. The activation of NF-kappaB has a key role in the immune homeostasis and the inflammatory response and therefore, in the pathogenesis of numerous diseases. Chondroitin sulfate (CS) is able to diminish NF-kappaB activation and nuclear translocation in chondrocytes and synovial membrane, effects that may explain the benefits of CS in osteoarthritis. In addition, systemic CS reduces NF-kappaB nuclear translocation in macrophages and hepatocytes, raising the hypothesis that CS might be of benefit to treat other diseases with a strong inflammatory component. There is preliminary evidence in humans that CS improves moderate to severe psoriasis. Moreover, experimental and clinical data suggest that CS might be a useful therapeutic agent in diseases such as inflammatory bowel diseases, atherosclerosis, Parkinson's and Alzheimer's diseases, multiple sclerosis, amyotrophic lateral sclerosis, rheumatoid arthritis and systemic lupus erythematosus.. These results urge for double blinded placebo-controlled trials to confirm the utility of CS in diseases with immune and inflammatory components.

Topics: Anti-Inflammatory Agents; Atherosclerosis; Chondroitin Sulfates; Humans; Inflammation; Inflammatory Bowel Diseases; Osteoarthritis; Psoriasis

The aim of the trial was to assess the efficacy of chondroitin sulphate (CS) on symptomatic knee osteoarthritis (OA) associated to psoriasis.. In this randomized, double-blind, placebo (PBO)-controlled clinical trial 129 patients with symptomatic knee OA and concomitant psoriasis were randomized into two groups receiving 800 mg daily of CS or PBO for 3 months. The primary efficacy outcome for knee OA was the Huskisson's visual analogue scale (VAS) and for psoriasis was the Psoriasis Area and Severity Index (PASI). Additionally, other secondary efficacy criteria for both conditions were assessed.. After 3 months of treatment, CS was more effective than PBO, relieving pain VAS (CS -26.9+/-24.8 vs PBO -14.23+/-20.8mm, P<0.01), decreasing the Lequesne index (CS -4.8+/-3.4 vs PBO -3.3+/-3.5, P<0.05) and reducing the number of patients using acetaminophen as rescue medication (CS 43% vs PBO 64%, P<0.05). Regarding PASI, Overall Lesion Severity Scale and Physician's Global Assessment of Change no statistically significant changes were detected in front of PBO. However, CS improved plantar psoriasis compared to PBO (CS 87% vs PBO 27%, P<0.05). Quality of life improved significantly in CS-treated patients according to the Short Form-36 health survey and the Dermatology Life Quality Index (DLQI). CS tolerability was excellent. Adverse events were infrequent and evenly distributed among groups. The incidence of psoriatic flares did not increase after treatments.. This study confirms the efficacy and safety of CS as a symptomatic slow-acting drug in patients with knee OA and shows that CS improves plantar psoriasis. The use of CS could represent a special benefit in patients with both pathologies since non-steroidal anti-inflammatory drugs have been reported to induce or exacerbate psoriasis.

Topics: Aged; Anti-Inflammatory Agents; Chondroitin Sulfates; Epidemiologic Methods; Female; Humans; Male; Middle Aged; Osteoarthritis, Knee; Pain Measurement; Psoriasis; Quality of Life; Treatment Outcome

We describe the clinical and histopathological results of plaque psoriasis in eleven adult patients with knee osteoarthritis and long-standing, moderate to severe psoriasis resistant to conventional therapy treated with chondroitin sulfate. Patients received 800 mg per day of chondroitin sulfate for 2 months. Skin biopsies were obtained before and after treatment. All patients but one presented a dramatic improvement of the condition of the skin, with a reduction of swelling, redness, flaking, and itching (clearance of psoriasis in one patient), increase in the hydration and softening of the skin, and amelioration of scaling. Histopathologically, there was a statistically significant decrease in epidermal thickness, a decrease in the thickness between the stratum basale and the stratum granulosum, a significant improvement of the degree of psoriasis activity, and a decrease in the number of keratinocytes stained with Ki-67. The confirmation of these serendipitous findings in controlled prospective studies could represent an important advance in the therapeutic armamentarium for patients with psoriasis given the excellent safety profile of chondroitin sulfate.

Topics: Administration, Oral; Adult; Aged; Anti-Inflammatory Agents; Chondroitin Sulfates; Female; Humans; Keratinocytes; Male; Middle Aged; Osteoarthritis; Psoriasis; Treatment Outcome

Chondroitin sulfates are implicated in epidermal biology, but functional significance of chondroitin sulfates remains unclear. Here, we report that chondroitin 6-sulfate is important for the maintenance of epidermal homeostasis. Mice deficient in chondroitin 6-O-sulfotransferase-1 (C6st-1), which is involved in biosynthesis of chondroitin 6-sulfate, exhibited keratinocyte hyperproliferation and impaired skin permeability barrier function. Chondroitin 6-sulfate directly interacted with the EGF receptor and negatively controlled ligand-induced EGF receptor signaling. Normal function of hyperproliferative C6st-1-knockout mouse-derived keratinocytes was rescued by treatment with exogenous chondroitin 6-sulfate. Epidermal hyperplasia, induced using imiquimod, was more severe in C6st-1-knockout mice than in C6st-1 wild-type mice. Taken together, these findings indicate that chondroitin 6-sulfate represses keratinocyte proliferation in normal skin, and that the expression level of C6st-1 may be associated with susceptibility to psoriasis.

Topics: Animals; Carbohydrate Sulfotransferases; Cell Proliferation; Cells, Cultured; Chondroitin Sulfates; Epidermis; Genetic Predisposition to Disease; HaCaT Cells; Humans; Keratinocytes; Mice; Mice, Knockout; Psoriasis; Skin; Sulfotransferases

Chondroitin sulfate (CS) is a natural glycosaminoglycan, formed by the 1-3 linkage of d-glucuronic acid to N-acetylgalactosamine, present in the extracellular matrix. It is used as a slow acting disease modifying agent in the treatment of osteoarthritis, and part of its beneficial effects are due to its antiinflammatory properties that result from an inhibitory effect on NF-κB signaling pathway. This ability raises the hypothesis that CS might be effective in other chronic inflammatory processes such as psoriasis, in which a deregulation of NF-κB is a key feature. In addition, psoriasis is characterized by an upregulation of STAT3 signaling pathway that is related to the epidermal hyperplasia. In the present study we report the pharmacological modulation of the NF-κB and STAT3 signaling pathways by CS in normal human keratinocytes. CS inhibited NF-κB activation and the release of some of the key psoriatic cytokines such as TNFα, IL-8, IL-6 and CCL27. Moreover, it impaired STAT3 translocation to the nucleus and significantly reduced STAT3 transcriptional activity by a mechanism that was independent from STAT3 phosphorylation. Our results confirm the interest of CS as a candidate for future drug research in the therapeutics of psoriasis given the need of more effective and safer oral medications for these patients.

Topics: Anti-Inflammatory Agents; Blotting, Western; Cells, Cultured; Chondroitin Sulfates; Dermoscopy; Electrophoretic Mobility Shift Assay; Humans; Keratinocytes; Microscopy, Fluorescence; NF-kappa B; Primary Cell Culture; Protein Binding; Psoriasis; STAT3 Transcription Factor

Interactions between proteins and glycosaminoglycans (GAGs) of the extracellular matrix are important to the regulation of cellular processes including growth, differentiation and migration. Understanding these processes can benefit greatly from the study of protein-GAG interactions using GAG oligosaccharides of well-defined structure. Materials for such studies have, however, been difficult to obtain because of challenges in synthetic approaches and the extreme structural heterogeneity in GAG polymers. Here, it is demonstrated that diversity in structures of oligosaccharides derived by limited enzymatic digestion of materials from natural sources can be greatly curtailed by a proper selection of combinations of source materials and digestive enzymes, a process aided by an improved understanding of the specificities of certain commercial preparations of hydrolases and lyases. Separation of well-defined oligosaccharides can then be accomplished by size-exclusion chromatography followed by strong anion-exchange chromatography. We focus here on two types of chondroitin sulfate (CS) as starting material (CS-A, and CS-C) and the use of three digestive enzymes with varying specificities (testicular hyaluronidase and bacterial chondroitinases ABC and C). Analysis using nuclear magnetic resonance and mass spectrometry focuses on isolated CS disaccharides and hexasaccharides. In all, 15 CS hexasaccharides have been isolated and characterized. These serve as useful contributions to growing libraries of well-defined GAG oligosaccharides that can be used in further biophysical assays.

Topics: Animals; Chondroitin Lyases; Chondroitin Sulfates; Hyaluronoglucosaminidase; Male; Oligosaccharides; Psoriasis; Sheep; Substrate Specificity; Testis

Chondroitin sulfate (CS) belongs to the group of glycosaminoglycans (GAGs), which are linear polysaccharides, located in the extracellular matrix and on the cell surface. To study the structure and distribution of CS in human skin and skin disorders, we have selected antibodies using phage display technique against CS. Four unique human anti-CS single-chain antibodies were selected: IO3D9, IO3H10, IO3H12, and IO4C2. We determined their amino acid sequence and evaluated their CS reactivity using ELISA and immunohistochemistry. Antibodies were reactive with CS, but not with other GAGs except for IO4C2, which was also reactive with heparin. Antibody IO3D9 showed a strong reactivity with highly sulfated CS (CSE). All antibodies displayed a different staining pattern in rat kidney, indicating the recognition of unique CS epitopes. In normal skin, the papillary dermis but not the reticular dermis was strongly stained. Antibody IO3H12 also stained basal keratinocytes. We applied these antibodies to study CS expression and localization in melanoma and psoriasis. A strong immunoreactivity with the extracellular matrix of melanoma metastases could be observed for all four antibodies, while in atypical nevi a less extensive reactivity with only the papillary dermis was observed. In psoriatic lesions, CS could be observed in the papillary dermis and in the reticular dermis, whereas the specific location in the papillary dermis found in normal skin was completely lost. In conclusion, human phage-display-derived anti-CS antibodies have been selected, characterized, and applied to detect CS alterations in skin conditions. Altered CS composition was detected in melanoma and psoriasis.

Topics: Antibodies; Chondroitin Sulfates; Epitopes; Humans; Melanoma; Psoriasis; Sensitivity and Specificity; Skin

Using a material consisting of related dermal specimens and 24-h urine samples from 17 psoriatics and 20 non-psoriatics it has been shown for the first time that the excretion of dermatan sulphate and a fraction of chondroitinase ABC resistant GAG ('heparan sulphate') are positively associated with the tissue content of the analytically identical glycosaminoglycans in dermis. The excretion of chondroitin 4/6 sulphate, total hydroxyproline and a peptide-bound fraction of this does not, however, mirror the tissue content of the corresponding constituents in dermis. There was no difference in the type of association between tissue and urine measurements in psoriatics and non-psoriatics. The results were analysed using multiple regression to avoid the unwanted effect of diverse concomitant variables (6 variables).

Topics: Chondroitin Lyases; Chondroitin Sulfates; Circadian Rhythm; Dermatan Sulfate; Glycosaminoglycans; Heparitin Sulfate; Humans; Hydroxyproline; Psoriasis; Skin; Uronic Acids

Primary irritant dermatitis includes an inflammatory process of connective tissue which is of general interest. For the first time this process has been characterised biochemically in humans by following the dermal changes in the concentration of hydroxyproline and four glycosaminoglycans. In healthy individuals (n = 7) and in psoriatics (n = 8) the changes were rather similar. Only dermatan sulphate showed a tendency towards an abnormal response in the psoriatics. In both groups the deviations from the pre-irritant condition clearly distinguished the response of irritant dermatitis from that of the wound healing process: (1) the concentration of hyaluronic acid decreased by the third day and remained so until by the sixth day, (2) after a decrease on the third day the concentration of dermatan sulphate returned to the initial value by the sixth day, (3 and 4) the concentration of chondroitin 4/6-sulphate and heparan sulphate increased continuously from the third to the sixth day, and (5) the concentration of hydroxyproline remained constant throughout the period of investigation.

Topics: Adult; Aged; Benzalkonium Compounds; Chondroitin Sulfates; Dermatan Sulfate; Dermatitis, Contact; Female; Glycosaminoglycans; Heparitin Sulfate; Humans; Hyaluronic Acid; Hydroxyproline; Male; Middle Aged; Psoriasis; Skin

The investigation included 17 psoriatics and 19 healthy controls. The content of sulphate per disaccharide unit (sulphate/uronic acid ratio) was measured in the sulphated glycosaminoglycans (GAGs) isolated from urine and dermal biopsies of the gluteal region. Biopsies were taken from both involved and uninvolved skin of the psoriatics. Perfectly normal sulphate/uronic acid ratios were found in the involved and uninvolved skin as well as in the urine of the psoriatics. A close and positive correlation between the sulphate/uronic acid ratio of the sulphated GAGs in the affected and unaffected skin of the psoriatics was discovered. The results are discussed in relation to earlier findings on the same specimens which shows that the concentration of sulphated GAGs in the psoriatic lesions is increased (28%) as is the urinary excretion of sulphated GAG in the same patients (62%).

Topics: Adult; Aged; Chondroitin Sulfates; Dermatan Sulfate; Female; Glycosaminoglycans; Heparitin Sulfate; Humans; Hyaluronic Acid; Male; Middle Aged; Psoriasis; Skin; Sulfates; Uronic Acids

The investigation included 15 psoriatic patients and 14 healthy controls. By using a simple method based on susceptibility to chondroitinases the excretion of dermatan sulphate, chondroitin-4/6-sulphate and heparan sulphate in the psoriatics was found to be increased with 104, 62 and 47% from uronic acid mean excretions of 1.97, 6.37 and 5.10 mumol/24 h, respectively. The excretion of hydroxyproline was not increased. In both groups the excretion of hyaluronic acid was insignificant. The absolute increase in the excretion of a major skin component like dermatan sulphate was exceeded by the excretion of chondroitin-4/6-sulphate and heparan sulphate which are both small components of skin. This indicates a comparatively high turnover of those two fractions in psoriatic lesions. The fact, that only the excretion of dermatan sulphate correlated with the fraction of skin surface involved in the psoriatic disease, indicated an important origin of this fraction, as well as the possibility of dermatan sulphate as a means of following dermal metabolism.

Topics: Adult; Aged; Chondroitin; Chondroitin Sulfates; Chondroitinases and Chondroitin Lyases; Dermatan Sulfate; Electrophoresis, Cellulose Acetate; Female; Heparitin Sulfate; Humans; Hyaluronic Acid; Hydroxyproline; Male; Middle Aged; Psoriasis