Category: Proteins & Peptides

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Reference: AG-40B-0235

Interleukin-12 (IL-12) family members are heterodimer glycoproteins, composed of two covalently linked subunits, alpha and beta chains. The alpha-subunit consists of IL-23p19, IL-27p28, and IL-12p35, and the beta-subunit includes IL-12p40 and Epstein-Barr virus-induced gene (Ebi3). IL-12 members bind to cognate heterodimeric receptor chains expressed on T cells. This family includes IL-12, IL-23, IL-27, IL-35 and IL-39. IL-12 and IL-23 are predominantly proinflammatory cytokines that contribute key roles in the development of Th1 and Th17 cells, respectively. IL-27 has both pro- and anti-inflammatory properties and is a potent T cell immunomodulator. IL-35, a new member of this family, is a potent inhibitory cytokine produced by natural, thymus-derived regulatory T cell (nTreg) populations. IL-39, the newest member of the IL-12 family, mediates the inflammatory response through the activation of STAT1/STAT3 signaling pathway. These IL-12 family members link innate immunity with the development of adaptive immunity and are also important for regulating T cell responses. Interleukin-23 (IL-23) is composed of the IL-12 p40 chain covalently linked to p19, a chain related to the IL-12 p35 subunit. IL-23 signals through the IL-23 receptor complex, which is composed of the IL-12Rbeta1 chain and a gp130-like chain, IL-23R. Triggering of the IL-23 receptor complex leads to the activation of Tyk2, Jak2 and STAT1, 3 and 4. IL-23 induces IFN-gamma production, Th1 cell differentiation and activation of the antigen-presenting functions of dendritic cells. IL-23 induces autoimmune inflammation and thus may be responsible for autoimmune inflammatory diseases and important for tumorigenesis. The protein IL-23 (mouse):Fc-KIH (human) (rec.) is produced by using two different vectors, one encoding for the IL-23A/p19:Fc Knobs sequence (synthesizing a protein of 55kDa) and one encoding for the IL-12B/p40:Fc Holes sequence (synthesizing a protein of 75kDa). Both vectors transfected into CHO cells produce both Fc molecules (Knobs-into-Holes technology; J.B. Ridgway, et al.; Protein Eng. 9, 617 (1996)) required for dimerization and for secretion of the final protein IL-23 (mouse): Fc-KIH (human) (rec.). InVivoKines™ are a new generation of recombinant fusion proteins for immunotherapeutic, preclinical and translational in vivo research, developed and manufactured by AdipoGen Life Sciences.

Reference: AG-40B-0236

Interleukin-12 (IL-12) family members are heterodimer glycoproteins, composed of two covalently linked subunits, alpha and beta chains. The alpha-subunit consists of IL-23p19, IL-27p28, and IL-12p35, and the beta-subunit includes IL-12p40 and Epstein-Barr virus-induced gene (Ebi3). IL-12 members bind to cognate heterodimeric receptor chains expressed on T cells. This family includes IL-12, IL-23, IL-27 and IL-35 and IL-39. IL-12 and IL-23 are predominantly proinflammatory cytokines that contribute key roles in the development of Th1 and Th17 cells, respectively. IL-27 has both pro- and anti-inflammatory properties and is a potent T cell immunomodulator. IL-35, a new member of this family, is a potent inhibitory cytokine produced by natural, thymus-derived regulatory T cell (nTreg) populations. IL-39, the newest member of IL-12 family, mediates the inflammatory response through the activation of STAT1/STAT3 signaling pathway. These IL-12 family members link innate immunity with the development of adaptive immunity and are also important for regulating T cell responses. IL-27 is composed of two subunits, IL-27p28 and Epstein-Barr virus-induced gene 3 (EBI3) signals via a heterodimeric receptor consisting of WSX-1 and glycoprotein (gp130), leading to activation of STAT 1 and 3. IL-27 is pro-inflammatory and promotes NK and T cell proliferation as well as the production of IFN-gamma. It is anti-inflammatory, inhibiting Th2 and Th17 cell activities and stimulating the production of IL-10 by T regulatory cells. IL-27 has potent antiviral activities against numerous viruses, by increasing the production of interferons (IFNs). Finally, IL-27 has antitumor activity as well as anti-angiogenic activity with activation of the production of anti-angiogenic chemokines. The protein IL-27 (mouse):Fc-KIH (human) (rec.) is produced by using two different vectors, one encoding for the IL-27A/p28:Fc Knobs sequence (synthesizing a protein of 62kDa) and one encoding for the IL27B/EBI3: Fc Holes sequence (synthesizing a protein of 60kDa). Both vectors transfected into CHO cells produce both Fc molecules (Knobs-into-Holes technology; J.B. Ridgway, et al.; Protein Eng. 9, 617 (1996)) required for dimerization and for secretion of the final protein IL-27 (mouse): Fc-KIH (human) (rec.). InVivoKines™ are a new generation of recombinant fusion proteins for immunotherapeutic, preclinical and translational in vivo research, developed and manufactured by AdipoGen Life Sciences.

Reference: AG-40B-0237

The V-set and transmembrane domain-containing protein (VSTM) family is composed of 8 proteins: VSTM1v1, VSTM1v2, VSTM2a, VSTM2b, VSTM2L, VSTM3, VSTM4 and VSTM 5. Members of the VSTM family are associated with the regulation of functions of immune cells, adipose cells and neuronal cells. The VSTM family is an immunoglobulin (Ig) superfamily that shares structural similarities with the B7-like transmembrane proteins involved in immune regulation. VSTM1 and VSTM4 play positive and negative roles in macrophage activation, respectively. VSTM3 (TIGIT) acts as a co-inhibitory receptor that suppresses the cytokine production of T cells and NK cells. V-set and transmembrane domain-containing protein 5 (Vstm5), a newly characterized small membrane glycoprotein highly expressed in the CNS, facilitates the formation of neuronal dendrites and protrusions such as dendritic filopodia. Regulatory roles of VSTM5 for in vitro and in vivo immune responses have been reported. VSTM5 functions as a novel immune checkpoint by regulating T cell proliferation and cytokine production, Treg generation by maintenance of T cell energy and possibly induction of T cell apoptosis.

Reference: AG-40B-0238

Interleukin-7 (IL-7) is a hematopoietic growth factor and a member of the IL-7/IL-9 family, which is produced by fetal liver cells, stromal cells in the bone marrow (BM), thymus and other epithelial cells, including keratinocytes and enterocytes. The receptor of IL-7, IL-7R, is a heterodimeric complex consisting of the alpha-chain (CD127) and the common cytokine receptor gamma-chain, shared with the receptors for IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21, and expressed in a variety of cells. IL-7 has a critical developmental function at every stage of T cell development, for both alphabeta and gammadelta lineages, and for the development and survival of naive T cells as well as generation and maintenance of CD4 and CD8 memory. IL-7 is also essential for the development and maintenance of the new ILCs. IL-7 is important throughout hematopoiesis, facilitating key lineage fate decisions. IL-7 is thought to support aberrant immune activity in autoimmune diseases such as diabetes and multiple sclerosis and in chronic inflammatory diseases such as rheumatoid arthritis, ankylosing spondylitis and inflammatory bowel disease. IL-7 contributes to leukemia development in vivo and also stimulates multiple immune-mediated mechanisms that contribute to the eradication of tumors. The protein IL-7 (human) (monomeric):Fc-KIH (human) (rec.) is produced by using two different vectors, one encoding for the IL-7 (human):Fc Knobs sequence (synthesizing a protein of 60kDa) and one encoding for the Fc Holes sequence (synthesizing a protein of 28kDa). Both vectors transfected into HEK293 cells produce both Fc molecules (Knobs-into-Holes technology; J.B. Ridgway, et al.; Protein Eng. 9, 617 (1996)) required for dimerization of the Fc moieties and for secretion of the final protein IL-7 (human) (monomeric):Fc-KIH (human) (rec.). InVivoKines™ are a new generation of recombinant fusion proteins for immunotherapeutic, preclinical and translational in vivo research, developed and manufactured by AdipoGen Life Sciences.

Reference: AG-40B-0010CSG

MultimericCD40L™ is a high-activity construct in which two trimeric CD40 ligands are artificially linked via the collagen domain of ACRP30. This construct very effectively simulates the natural membrane-assisted aggregation of CD40L in vivo. It provides a simple and equally potent alternative to [CD40L+enhancer] combinations. MultimericCD40L™ has been shown to suppress alum-induced IL-1beta release and caspase-1 activation in a dose-, CD40- and time-dependent manner, without affecting BMDM viability. It also effectively suppressed the inflammasome function triggered by NLRP3 activators. The secretion of caspase-1 independent inflammatory mediators has been shown to be unaltered or even enhanced. MultimericCD40L™ has been shown to be a potent tool for B cell expansion. It also has big potential as a growth factor for tumor-infiltrating lymphocytes (TILs), which have been shown to be important for T cell therapy.

Reference: AG-40B-0239

The V-set and transmembrane domain-containing protein (VSTM) family is composed of 8 proteins: VSTM1v1, VSTM1v2, VSTM2a, VSTM2b, VSTM2L, VSTM3, VSTM4 and VSTM 5. Members of the VSTM family are associated with the regulation of functions of immune cells, adipose cells and neuronal cells. The VSTM family is an immunoglobulin (Ig) superfamily that shares structural similarities with the B7-like transmembrane proteins involved in immune regulation. VSTM1 and VSTM4 play positive and negative roles in macrophage activation, respectively. VSTM3 (TIGIT) acts as a co-inhibitory receptor that suppresses the cytokine production of T cells and NK cells. V-set and transmembrane domain-containing protein 5 (Vstm5), a newly characterized small membrane glycoprotein highly expressed in the CNS, facilitates the formation of neuronal dendrites and protrusions such as dendritic filopodia. Regulatory roles of VSTM5 for in vitro and in vivo immune responses have been reported. VSTM5 functions as a novel immune checkpoint by regulating T cell proliferation and cytokine production, Treg generation by maintenance of T cell energy and possibly induction of T cell apoptosis.

Reference: AG-40B-0240

Interleukin-12 (IL-12) family members are heterodimer glycoproteins, composed of two covalently linked subunits, alpha and beta chains. The alpha-subunit consists of IL-23p19, IL-27p28 and IL-12p35, and the beta-subunit includes IL-12p40 and Epstein-Barr virus-induced gene (Ebi3). IL-12 members bind to cognate heterodimeric receptor chains expressed on T cells. This family includes IL-12, IL-23, IL-27, IL-35 and IL-39. IL-12 and IL-23 are predominantly proinflammatory cytokines that contribute key roles in the development of Th1 and Th17 cells, respectively. IL-27 has both pro- and anti-inflammatory properties and is a potent T cell immunomodulator. IL-35, a new member of this family, is a potent inhibitory cytokine produced by natural, thymus-derived regulatory T cell (nTreg) populations. IL-39, the newest member of IL-12 family, mediates the inflammatory response through the activation of STAT1/STAT3 signaling pathway. These IL-12 family members link innate immunity with the development of adaptive immunity and are also important for regulating T cell responses. IL-12 is composed of two subunits IL-12A/p35 and IL-12B/p40 and signals via a high-affinity IL-12R, leading to activation of STAT 4. IL-12 is produced by macrophages, dendritic cells and B cells. The key role of the pro-inflammatory IL-12 is to induce the IFN-gamma which regulates the Th responses, to promote the naïve T cells to directly differentiate into effector cells (Th1) and then release IFN-gamma. The protein IL-12 (mouse):Fc-KIH (human) (rec.) is produced by using two different vectors, one encoding for the IL-12A/p35:Fc Knobs sequence (synthesizing a protein of 60kDa) and one encoding for the IL12B/p40:Fc Holes sequence (synthesizing a protein of 75kDa). Both vectors transfected into CHO cells produce both Fc molecules (Knobs-into-Holes technology; J.B. Ridgway, et al.; Protein Eng. 9, 617 (1996)) required for dimerization and for secretion of the final protein IL-12 (mouse):Fc-KIH (human) (rec.). InVivoKines™ are a new generation of recombinant fusion proteins for immunotherapeutic, preclinical and translational in vivo research, developed and manufactured by AdipoGen Life Sciences.

Reference: AG-40B-0241

IL-38 (IL-1F10) belongs to the IL-1 family of proteins. IL-38 is expressed in heart, placenta, fetal liver, spleen, thymus and tonsil. The expression in a variety of immune tissues and similarity to IL-1Ra suggest a role of IL-38 in the inflammatory response. It has been reported that removal of the N-terminus domain of the interleukins of the IL-1F family such as IL-1F5 / 6 / 8 or 9 (also called IL-36Ra, IL-36alpha, IL-36beta or IL-36gamma) is important to increase their biological activity. Recently it has been shown that IL-38 is N-terminally processed and secreted by apoptotic cells. Released processed IL-38 (20-152) binds to the receptor Interleukin-1 receptor accessory protein-like 1 (IL1RAPL1; TIGIRR-2) at the surface of macrophages. Processed IL-38-activated IL1RAPL1 reduces the production of IL-6 leading to inflammation attenuation. IL-38 is unregulated during some autoimmune diseases such as Systemic Lupus Erythematosus. The protein IL-38 (aa 1-152) (human) (monomeric):Fc-KIH (human) (rec.) is produced by using two different vectors, one encoding for the IL-38 (aa 1-152) (human):Fc Knobs sequence (synthesizing a protein of 45kDa) and one encoding for the Fc Holes sequence (synthesizing a protein of 28kDa). Both vectors transfected into HEK293 cells produce both Fc molecules (Knobs-into-Holes technology; J.B. Ridgway, et al.; Protein Eng. 9, 617 (1996)) required for dimerization of the Fc moieties and for secretion of the final protein IL-38 (aa 1-152) (human)(monomeric):Fc-KIH (human) (rec.). InVivoKines™ are a new generation of recombinant fusion proteins for immunotherapeutic, preclinical and translational in vivo research, developed and manufactured by AdipoGen Life Sciences.

Reference: AG-40B-0242

Grancalcin is a member of a new family of proteins named penta-EF-hand (PEF), which contains five repetitive EF hand motifs. PEF proteins form a unique group including calpain, sorcin, grancalcin, ALG-2 (apoptosis-linked gene-2 protein) and peflin. The penta-EF hand members are Ca2+-binding proteins implicated in regulating cell migration, apoptosis and the mobilization of immune cells. Senescent cells accumulate in the bone marrow and secrete factors, termed senescence-associated secretory phenotype (SASP), that can promote skeletal aging. Recently, senescent neutrophils and macrophages in the bone marrow were shown to be critical cell types during skeletal aging releasing Grancalcin (GCA) to promote such aging. Grancalcin seems to act by competitively binding to and inactivating PlexinB2 functions in bone marrow stromal cells (BMSCs) leading to repression of osteogenesis and increase of adipogenesis. Increased Grancalcin expression in immune cells (bone marrow macrophages and in neutrophils) is due to higher endotoxin levels observed during aging.

Reference: AG-40B-0243

Flagellin is the subunit protein which polymerizes to form the filaments of bacterial flagella. It activates the innate immune system through the receptor Toll-like Receptor 5 (TLR5) and the intracellular protein NLRC4 (NLR family CARD domain-containing protein 4).

Reference: AG-40B-0102

Irisin is a recently described exercise-induced hormone secreted by skeletal muscle in mice and humans. Irisin activates beige fat cells (beige cells have a gene expression pattern distinct from either white or brown fat and are preferentially sensitive to the polypeptide hormone Irisin). Irisin is cleaved from the type I membrane protein FNDC5 and improves systemic metabolism by increasing energy expenditure.

Reference: AG-40B-0244

The Insulin-growth factor-like gene family is a new family of proteins consisting of four proteins in humans (IGFL1 to 4) and one in mice (mIGFL). mIGFL is expressed in normal skin in mice and further upregulated during inflammation responses in the skin or after skin wounding. In humans only IGFL1 expression is increased in psoriatic skin samples. mIGFL and human IGFL1 and 3 interact with specificity and high affinity to a novel receptor named IGF-like family receptor 1 (formerly TMEM-149). Analysis of the amino acid sequence of IGFLR1 indicated that this receptor is likely a novel member of the TNF-R family. IGFLR1 is expressed most abundantly on mouse T cells, suggesting that mIGFL and IGFL1 produced in the skin may potentially exert regulatory functions on T cell responses. In addition to the ovary, spinal cord and fetal skin, IGFL1 is also expressed in head and neck tumors, uterine tumors, squamous cell carcinomas and lung adenocarcinoma. In many cancers, IGFL1 (as well as the other IGFLs) plays multiple roles in regulating the proliferation, differentiation and apoptosis of cancer cells.