IP-10

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IP-10 Andrew D. Luster* Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA * corresponding author tel: 617-726-5710, fax: 617-726-5411, e-mail: [email protected] DOI: 10.1006/rwcy.2000.10007.

SUMMARY

Structure

IP-10 is a CXC chemokine that is induced from most cells in response to both type I and type II interferon stimulation and LPS. IP-10 is chemotactic for activated T cells and NK cells by binding to and activating CXCR3. IP-10 also has antiangiogenic and antitumor activity in vivo. IP-10 expression has been seen in many TH1-type human inflammatory diseases and plays an important role in recruiting activated effector T cells into sites of tissue inflammation.

IP-10 is a 77 amino acid secreted nonglycosylated protein (Luster and Ravetch, 1987a). It contains four cysteines in the mature protein with the first two cysteines separated by an amino acid. IP-10 lacks the ELR sequence preceding the first cysteine typical of IL-8 and other CXC chemokines active on neutrophils, and hence it is a member of the non-ELR CXC chemokine family. The N-terminus of IP-10 has been identified as valine from protein purified from endothelial cells (Luster and Ravetch, 1987a) and tumor cells (Proost et al., 1993) and IP-10 is known to be biologically active in this form. IP-10 is a basic protein and binds heparin with relatively high affinity (25 nM) (Luster et al., 1995).

BACKGROUND

Discovery Human IP-10 was discovered as an mRNA that was highly induced in the human monocytic cell line U937 by IFN using differential colony hybridization (Luster et al., 1985). This mRNA encoded a 10 kDa protein and was therefore named IP-10 for interferoninducible protein of 10 kDa. Using a similar approach, mouse IP-10 was independently discovered by two groups as a gene induced in monocytes by activated T cell supernatants (Vanguri and Farber, 1990) and by LPS (Ohmori and Hamilton, 1990). Rat IP-10 was identified as a gene induced in fibroblasts by transformation with Ha-ras and p53 (Liang et al., 1994) and independently identified as an mRNA induced in LPS-stimulated carotid arteries (Wang et al., 1996).

Main activities and pathophysiological roles IP-10 is chemotactic for activated T cells and NK cells (Maghazachi et al., 1997; Taub et al., 1993). IP-10 is thought to play an important role in recruiting T cells, activated in regional lymph nodes, into sites of inflammation and infection. IP-10 also inhibits angiogenesis and tumor growth in vivo (Luster and Leder, 1993; Angiolillo et al., 1995; Luster et al., 1995; Arenberg et al., 1996).

Alternative names

GENE AND GENE REGULATION

When they were identified, mouse IP-10 was called crg-2 (Vanguri and Farber, 1990) and rat IP-10 was called mob-1 (Liang et al., 1994). The gene name is SCYB10 and the consensus nomenclature name is CXCL10.

Accession numbers Human: X02530 Mouse: M33266, M86829 Rat: U17035, U22520

1104 Andrew D. Luster

Chromosome location The human IP-10 gene was mapped to 4q21.2 by in situ hybridization (Luster et al., 1987). Mouse IP-10 was mapped to chromosome 5.

Figure 1 Amino acid sequence for human IP-10. MNQTAILICC LIFLTLSGIQ GVPLSRTVRC TCISISNQPV NPRSLEKLEI IPASQFCPRV EIIATMKKKG EKRCLNPESK AIKNLLKAVS KEMSKRSP

Sequence Relevant linkages An analysis of P1 clones revealed that IP-10 is linked head to tail to MIG, another non-ELR CXC chemokine with which it shares 37% identity, with their start codons separated by