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MIP-4/CCL18 Protein, Human

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MIP-4/CCL18 Protein, Human is a CC chemokine ligand that binds to PITPNM3, GPR30 and CCR8 receptors and also acts as a neutral CCR3 antagonist mediating inflammation, autoimmunity and carcinogenesis. MIP-4/CCL18 Protein, Human is a recombinant human MIP-4/CCL18 (A21-A89) protein expressed by E. coli.

For research use only. We do not sell to patients.
  • Species: Human
  • Source: E. coli
  • Storage:
    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.
  • MIP-4/CCL18 Protein, Human Product Image
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  • Biological Activity
  • Technical Parameters
  • Product Properties
  • Documentation
  • References
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Biological Activity

Description

MIP-4/CCL18 Protein, Human is a CC chemokine ligand that binds to PITPNM3, GPR30 and CCR8 receptors and also acts as a neutral CCR3 antagonist mediating inflammation, autoimmunity and carcinogenesis. MIP-4/CCL18 Protein, Human is a recombinant human MIP-4/CCL18 (A21-A89) protein expressed by E. coli[1][2].

Background

CCL18, also known as macrophage inflammatory protein-4 (MIP-4), pulmonary and activation-regulated chemokine (PARC), dendritic cell (DC)-chemokine 1 (DC-CK1) and alternative macrophage activation-associated CC chemokine-1 (AMAC-1), is a small cell factor of the CC chemokine family. CCL18 is located on chromosome 17 in the human gene and has the highest amino acid identity (65%) with CCL3, encoding an 89 amino acid long protein with a 20 amino acid long peptide signal sequence at the N' terminus that signals its secretion and is cleaved in the endoplasmic reticulum into a 69 amino acid long mature protein[1]. CCL18 is mainly produced by antigen-presenting cells of the innate immune system, including dendritic cells, monocytes and macrophages, but not in T and B cells. In macrophages, CCL18 is induced by the Th2 cytokines IL-4 and IL-13, which program macrophages to differentiate into AAMs, which contribute to the healing phase of acute inflammatory responses and to tissue remodeling and fibrosis in chronic inflammatory diseases.CCL18 can bind to PITPNM3, GPR30, and CCR8 receptors, where CCL18 binding to CCR8 binding induces chemotaxis of Th2 cells. In addition, CCL18 can also act as a neutral CCR3 antagonist and participate in the inflammatory response. It has been shown that CCL18 and its receptor CCR8 are co-expressed in diseased human tissues during active eosinophilic inflammation. In parallel, enhanced production of CCL18 has been demonstrated in a variety of diseases, including various malignancies and inflammatory joint, lung and skin diseases[2].

In Vitro

CCL18 (20 ng/mL, 12-48 h) promotes HUVEC angiogenesis and enhances HUVEC migration without enhancing proliferation, while blocking the effect of CCL18 with a neutralizing anti-CCL18(10 μg/mL) antibody inhibits tumor-associated macrophages(TAM)-dependent HUVEC migration in a concentration-dependent manner[3].
CCL18 (50 or 100 ng/mL, 36 h) results in significantly lower E-cadherin expression levels and higher MMP-2 and VEGF-C expression levels compared to controls, also can promote migration and invasion via CCR8 in bladder cancer cells[4].

Verified Bioactivity

1.Full biological activity determined by a chemotaxis bioassay using human T-lymphocytes is in a concentration of 1.0-10 ng/mL.
2.Measured by its ability to inhibit Eotaxin-induced chemotaxis of BaF3 mouse pro-B cells transfected with human CCR3. The ED50 for this effect is 2.142 μg/mL.

Technical Parameters

  • Species Human
  • Source E. coli
  • Tag Tag Free
  • Accession

    P55774 (A21-A89)

  • Gene ID
    6362  [NCBI]
  • Molecular Construction
    • N-term
    • CCL18 (A21-A89)
      Accession # P55774
    • C-term
  • Protein Length

    Full Length of Mature Protein

  • Synonyms

    CCL18; Macrophage Inflammatory Protein 4; Prev. SCYA18; C-C Motif Chemokine 18; DC-CK1; CC Chemokine PARC; AMAC-1; AMAC1; DCCK1; Pulmonary And Activation-Regulated; MIP-4; Chemokine (C-C Motif) Ligand 18; PARC; Small Inducible Cytokine A18; CKb7; Small-In

  • AA Sequence

    AQVGTNKELCCLVYTSWQIPQKFIVDYSETSPQCPKPGVILLTKRGRQICADPNKKWVQKYISDLKLNA

  • Predicted Molecular Mass

    7.9 kDa

  • Molecular Weight

    Approximately 9 kDa, based on SDS-PAGE under reducing conditions.

  • Purity

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

Product Properties

Appearance

Lyophilized powder

Formulation

1.Lyophilized from a 0.22 μm filtered solution of 20 mM PB, 100 mM NaCl, pH 7.4.
2.Lyophilized from a 0.22 μm filtered solution of PBS, pH 7.4, 8% trehalose.
Please refer to the lot-specific COA for specific buffer information.

Endotoxin Level

<1 EU/μg, determined by LAL method.

Reconstitution

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).

Storage & Stability

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.

Shipping

Room temperature in continental US; may vary elsewhere.

References

[1]. K Hieshima, et al. A novel human CC chemokine PARC that is most homologous to macrophage-inflammatory protein-1 alpha/LD78 alpha and chemotactic for T lymphocytes, but not for monocytes. J Immunol. 1997 Aug 1;159(3):1140-9. [Content Brief]

[2]. Schutyser E, et al. Involvement of CC chemokine ligand 18 (CCL18) in normal and pathological processes. J Leukoc Biol. 2005 Jul;78(1):14-26. [Content Brief]

[3]. Sabina A Islam, et al. Identification of human CCR8 as a CCL18 receptor. J Exp Med. 2013 Sep 23;210(10):1889-98. [Content Brief]

[4]. Ling Lin, et al. CCL18 from tumor-associated macrophages promotes angiogenesis in breast cancer. Oncotarget. 2015 Oct 27;6(33):34758-73. [Content Brief]

[5]. Xiaoqiang Liu, et al. CCL18 enhances migration, invasion and EMT by binding CCR8 in bladder cancer cells. Mol Med Rep. 2019 Mar;19(3):1678-1686. [Content Brief]

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Calculators

Reconstitution Calculator

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The Specific Activity Calculator Equation
  • Specific Activity (Unit/mg)
  • Biological Activity (ED50)

Specific Activity (Unit/mg) = 106 ÷ Biological Activity (ED50)

Specific Activity (Unit/mg) Specific Activity (Unit/mg)
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MOQ
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100 mg

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Measured by its ability to inhibit anti-CD3-induced proliferation of stimulated CTLL-2 mouse cytotoxic T cells. The ED50 this effect is 0.8023 μg/ml, corresponding to a specific activity is 1246.42 units/mg.

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