TL1A/TNFSF15 Trimer Protein, Human (HEK293, His-Flag)

The TL1A protein (VEGI protein), belongs to the tumor necrosis factor (TNF) family and is a receptor for TNFRSF25 and TNFRSF6B. TL1A is involved in the activation of NF-κB and C-Jun pathways, which can be used as a regulator of mucosal immunity and participate in the immune pathway of inflammatory bowel disease (IBD) pathogenesis^[1][2]. TL1A originates from endothelial cells and inhibits the proliferation of breast cancer, epithelial and myeloid tumor cells^[3]. The human TL1A protein has a transmembrane domain (36-56 a.a.) that can be cleaved into membrane-type and soluble peptide fragments. TL1A/TNFSF15 Trimer Protein, Human (HEK293, His-Flag) is the extracullar part of TL1A protein (D91-L251), produced in HEK293 cells with N-terminal His- and Flag-tag.

TL1A (Tumor necrosis factor-like cytokine 1A), also known as TNF ligand-related molecule 1 and vascular endothelial cell growth inhibitor (VEGI), is the receptor for TNFRSF25 and TNFRSF6B, acts as a regulator of mucosal immunity and participates in immunological pathways involved in the inflammatory bowel diseases (IBD) pathogenesis^[1]. TL1A belongs to the tumor necrosis factor family, derived from endothelial cell. It is a ligand for DR3 and decoy receptor TR6/DcR3, the interaction with DR3 promotes T cell expansion during an immune response, whereas TR6 has an opposing effect. Moreover, DR3 is the death domain-containing receptor, that is upregulated during T cell activation. TL1A shows an inducible expression by TNF and IL-1alpha, and induces NF-kappaB activation and apoptosis in DR3-expressing cell lines. Meanwhile, TL1A acts as a costimulator that increases IL-2 responsiveness and secretion of proinflammatory cytokines^[2]. In addition, TL1A activates c-Jun N-terminal kinase. TL1A also activates caspase-3 leading to PARP cleavage, and inhibits the proliferation of breast carcinoma, epithelial, and myeloid tumor cells. TL1A promotes proliferation of normal human fibroblast cells. These results suggest that VEGI, a new member of the TNF family, has a signaling pathway similar to TNF and is most likely a multifunctional cytokine^[3]. Human TL1A protein has two glycosylated domains and one transmembrane domain (36-56 a.a.), and can be cleaved into membrane-type peptide fragments and soluble peptide fragments. The protein sequence of human is much different from mouse and rat with similarities of 68.42% and 70.45%, respectively.

TL1A (100 ng/mL; 15 min) interacts with TR6-Fc, results in NF-κB activation^[2].
TL1A (72-251 a.a.; 100 ng/mL; 72 h) increases IL-2 responsiveness and induces cytokine release in anti-CD3- and anti-CD28-treated T cells^[2].
TL1A (1 μg/mL; 12-24 h) induces IκB degradation in U-937 cells^[3].

TL1A (human, 72-251 a.a.; 3 mg/kg; i.v.; daily for 5 d) enhances in vivo and ex vivo splenic alloactivation in C57BL/6 mice^[2].

1.Immobilized Human TNFSF15 Trimer His at 0.5 μg/mL (100 μL/Well) on the plate. Dose response curve for Anti-TNFSF15 Antibody hFc with the EC₅₀ of 10.2-18.7 ng/mL determined by ELISA.
2.Immobilized Human TNFSF15 Trimer, His Tag at 1 μg/mL (100 μl/Well) on the plate. Dose response curve for Anti-TNFSF15 Antibody, hFc Tag with the EC₅₀ of ≤4 ng/mL determined by ELISA.
3.Measured by its binding ability in a functional ELISA. Immobilized Huamn TNFSF15 Trimer at 2 μg/mL (100 μL/Well) can bind Anti-TNFSF15 Antibody. The ED₅₀ for this effect is ≤4 ng/mL.

• 
  Measured by its binding ability in a functional ELISA. Immobilized Human TNFSF15 Trimer at 1 μg/mL (100 μL/Well) can bind Anti-TNFSF15 Antibody. The ED₅₀ for this effect is 3.112 ng/mL.

Human

HEK293

N-Flag;N-6*His

O95150-1 (D91-L251)

9966  [NCBI]

Partial

DGDKPRAHLTVVRQTPTQHFKNQFPALHWEHELGLAFTKNRMNYTNKFLLIPESGDYFIYSQVTFRGMTSECSEIRQAGRPNKPDSITVVITKVTDSYPEPTQLLMGTKSVCEVGSNWFQPIYLGAMFSLQEGDKLMVNVSDISLVDYTKEDKTFFGAFLL

Approximately 60-80 kDa, based on SDS-PAGE under reducing conditions, due to the glycosylation.

• 
  ≥ 95%, as determined by reducing SDS-PAGE.

Lyophilized powder

Lyophilized from a 0.22 μm filtered solution of PBS, pH 7.4.

<1 EU/μg, determined by LAL method.

It is not recommended to reconstitute to a concentration less than 100 μg/mL in ddH₂O. For long term storage it is recommended to add a carrier protein (0.1% BSA, 5% HSA, 10% FBS or 5% Trehalose).

Stored at -20°C for 2 years from date of receipt. After reconstitution, it is stable at 4°C for 1 week or -20°C for longer (with carrier protein). It is recommended to freeze aliquots at -20°C or -80°C for extended storage.

Room temperature in continental US; may vary elsewhere.

• [1]. Furfaro F, et al. TL1A: A New Potential Target in the Treatment of Inflammatory Bowel Disease. Curr Drug Targets. 2021;22(7):760-769.  [Content Brief]

  [2]. Migone TS, et al. TL1A is a TNF-like ligand for DR3 and TR6/DcR3 and functions as a T cell costimulator. Immunity. 2002 Mar;16(3):479-92.  [Content Brief]

  [3]. Haridas V, et al. VEGI, a new member of the TNF family activates nuclear factor-kappa B and c-Jun N-terminal kinase and modulates cell growth. Oncogene. 1999 Nov 11;18(47):6496-504.  [Content Brief]