A novel monoclonal antibody cross-reactive with both human and mouse α9 integrin useful for therapy against rheumatoid arthritis.

This study introduces a novel monoclonal anti-α9 integrin antibody (MA9-413) with human variable regions, isolated by phage display technology. MA9-413 specifically binds to both human and mouse α9 integrin by recognizing a conserved loop region designated as L1 (amino acids 104-122 of human α9 integrin). MA9-413 inhibits human and mouse α9 integrin-dependent cell adhesion to ligands and suppresses synovial inflammation and osteoclast activation in a mouse model of arthritis.

AS2762900-00, a potent anti-human IL-23 receptor monoclonal antibody, prevents epidermal hyperplasia in a psoriatic human skin xenograft model.

Interleukin (IL)-23 is thought to be critical in the pathogenesis of psoriasis, and anti-IL-23 monoclonal antibodies (mAbs) have been approved for the treatment of psoriasis. We speculated that an anti-IL-23 receptor mAb might have greater efficacy than an anti-IL-23 mAb in the treatment of local inflamed lesions with high IL-23 levels. We previously generated an anti-human IL-23 receptor mAb, AS2762900-00, which potently blocked IL-23-induced cell proliferation, regardless of the concentration of IL-23.

Generation and characterization of a potent fully human monoclonal antibody against the interleukin-23 receptor.

Interleukin (IL)-12 and IL-23 share a common subunit (p40) and function in T-helper (Th) 1 and Th17 immunity, respectively. Anti-IL-12/23p40 and specific anti-IL-23 antibodies are currently in clinical use for psoriasis and undergoing trials for autoimmune diseases. Since expression levels of the IL-23 receptor are likely to be much lower than those of IL-23, an anti-IL-23 receptor antibody might offer greater promise in inhibiting the IL-23-IL-17 pathways involved in inflammatory disorders.

Anti-IL-23 receptor monoclonal antibody prevents CD4 T cell-mediated colitis in association with decreased systemic Th1 and Th17 responses.

Experimental colitis studies, including T cell-mediated colitis, indicate that IL-23 rather than IL-12 orchestrates intestinal inflammation in inflammatory bowel disease (IBD). Previous studies have identified the roles of IL-12 and IL-23 using mice deficient for their specific subunits, p35 and p19, respectively. However, these studies do not completely reflect the difference in roles between IL-12 and IL-23, especially since the discovery of novel IL-12 family cytokines, which also include p35 or p19 subunits.

Tamsulosin potently and selectively antagonizes human recombinant α(1A/1D)-adrenoceptors: slow dissociation from the α(1A)-adrenoceptor may account for selectivity for α(1A)-adrenoceptor over α(1B)-adrenoceptor subtype.

We determined the binding affinity of tamsulosin, a selective α(1)-adrenoceptor antagonist, for human α(1)-adrenoceptor subtypes in comparison with those of other α(1)-adrenoceptor antagonists including silodosin, prazosin, 5-methylurapidil, terazosin, alfuzosin, nafopidil, urapidil and BMY7378. The association and dissociation kinetics of [(3)H]tamsulosin for recombinant human α(1)-adrenoceptor subtypes were compared with those of [(3)H]prazosin. Tamsulosin competitively inhibited [(3)H]prazosin binding to human α(1A)-, α(1B)- and α(1D)-adrenoceptors (pK(i) values were 10.

A novel, selective, and orally available antagonist for CC chemokine receptor 3.

CC chemokine ligand 11 (CCL11/eotaxin) and other CC chemokine receptor 3 (CCR3) ligands (CCL24/eotaxin-2, CCL26/eotaxin-3, CCL13/monocyte chemotactic protein-4, etc.) play important roles in the chemotaxis and activation of eosinophils and other CCR3-expressing cells (basophils, mast cells, and CD4(+) T helper 2 cells) in allergic inflammation incidents, including asthma and rhinitis. A newly synthesized compound, N-{(3R)-1-[(6-fluoro-2-naphthyl)methyl]pyrrolidin-3-yl}-2-{1-[(5-hydroxy-3-methylpyridin-2-yl)carbonyl]piperidin-4-ylidene}-acetamide hemifumarate (YM-355179), inhibited the binding of CCL11 and CCL5/regulated on activation normal T cell expressed and secreted to CCR3-expressing B300-19 cells with IC(50) values of 7.

Effects of interleukin-11 on the hematopoietic action of granulocyte colony-stimulating factor.

Interleukin-11 (IL-11, CAS 145941-26-0) is a cytokine that ameliorates thrombocytopenia induced by chemotherapy. Granulocyte colony-stimulating factor (G-CSF) is frequently used clinically as an adjuvant therapy to ameliorate neutropenia. In this study, it has been investigated whether IL-11 influences the hematopoietic action of G-CSF in vitro.

Recombinant human interleukin-11 improved carboplatin-induced thrombocytopenia without affecting antitumor activities in mice bearing Lewis lung carcinoma cells.

Purpose: Interleukin-11 (IL-11) is a stromal cell derived multifunctional cytokine, which plays important roles in the hematopoietic and nonhematopoietic systems. Recombinant human IL-11 (rhIL-11) is used in the treatment of chemotherapy-induced thrombocytopenia. We have investigated the effects of rhIL-11 on the antitumor activity of chemotherapeutic agents and on thrombocytopenia in myelosuppressed mice bearing tumor cells.

Fertilization Membrane Formation in Sea Urchin Eggs Induced by Drugs Known to Cause Ca Release from Isolated Sarcoplasmic Reticulum: (sea urchin egg/fertilization membrane/ryanodine/micronazole/procaine).

Ryanodine, miconazole, clotrimazole, doxorubicin, quercetin, halothane, caffeine and chloroform, which activate Ca -induced Ca release from Ca stores, induced Ca release from a particulate fraction isolated from sea urchin eggs, Ca influx into eggs and formation of a fertilization membrane in an appreciable number of eggs. Their minimum effective concentrations for inducing a fertilization membrane increased in the order of these drugs listed above, and this order was also the same as that of their minimum effective concentrations for inducing Ca release from the isolated particulate fraction. Their effect in inducing a fertilization membrane was blocked by ruthenium red and procaine, which inhibit Ca release from Ca stores.