• 한국생물공학회:학술대회논문집
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• 2001.11a
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• pp.775-778
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• 2001

Chemokines are small chemotalic cytokines that have a number of biological functions. Some chemokines regulate the proliferation of hematopoietic stem and progenitor cells(HSPC). Leukotactin-l(Lkn-l) is a CC chemokine and is known to reduce colony forming unit(CFU). The N-terminal truncated Leukotactin-l(rtLkn-l), produced by Pichia pastoris, suppressed CFU from 40 to 60%. The rtLkn-l protected CFU from cytotoxic effect of anticancer drug such as Ara-C, doxorubicin, cyclophosphamide and 5-FU by cell cycle arrest.

• Biotechnology and Bioprocess Engineering:BBE
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• v.9 no.1
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• pp.1-6
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• 2004

The human chemokine, the short version of leukotactin-1(shLkn-1;molecular weight=7.2 kD and 66 amino acids), was expressed and secreted into a culture medium using the me-thylotrophic yeast, Pichia pastoris. The recombinant shLkn-1 was purified from the culture supernatant using a simple two-step procedure consisting of cation exchange and reverse phase chromatography(RPC), in which shLkn-1 was highly purified (99.5%) with a high recovery yield of 82.7%. The C-terminal truncated derivative of shLkn-1 was found in the supernatant and was separated by RPC. The physicochemical properties of the purified shLkn-1 were verified to be the same as expected. The biological activity of the purified recombinant shLkn-1 was also quantified using a chemotaxis assay. It was observed that the recombinant shLkn-1 had the maximum migration activity at a concentration of 10nM, as potent as MIP-1${\alpha}$.

• Biotechnology and Bioprocess Engineering:BBE
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• v.9 no.1
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• pp.7-11
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• 2004

Leukotactin-1 (Lkn-1), a human CC chemokine, has been demonstrated to induce chemotaxis of neutrophils, monocytes, eosinophils and Iym phocytes and has been shown to suppress colony formation of hematopoietic stem and progenitor cells (HSPC) in vitro and in vivo. The temporal suppression of HSPC by chemokines could potentially be applicable for various indications, such as the protection of HSPC from the several anti-proliferating chemotherapeutics in cancer treatments. In order to evaluate the protective effects on myeloid progenitor cells, the recombinant Lkn-1 was produced by Pichia pastoris and tested with cyclophosphamide, cytotoxic chemotherapeutics. The pretreatment of Lkn-1 increased the number of HSPC in bone marrow as well as the potency of resulting progenitor cells after the treatment of cyclophosphamide. Af-ter the first cycle of cyclophosphamide treatment these protections of HSPC correlated with the increased number of white blood cells and neutrophils in the peripheral blood. In lethal conditions created by the repeated administration of cyclophosphamide, the treatment of Lkn-1 enhanced the survival of mice, suggesting the potential use of Lkn-1 as the protective agent for HSPC from various cytotoxic insults.

• Biomedical Science Letters
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• v.12 no.3
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• pp.145-151
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• 2006

Leukotactin-l (Lkn-l )/CCL15 has been known as a potent chemoattractant of leukocytes. However, the precise function of Lkn-l in human neutrophils has not been explained well. In the present study, we investigated the contribution of Lkn-1 in chemotactic activity of human neutrophils. Both CCR1 and CCR3 mRNA expressions are strongly expressed in human neutrophils but CCR2 protein expression was uniquely detected on the cell surface. Lkn-l binding to CCR1 and CCR3 induced chemotactic activity of neutrophils. Chemotactic index of Lkn-l was comparable to that of IL-8. $MIP-1{\alpha}/CCL3$ binding to CCR1 and CCR5 has no effect on neutrophil migration. Cell migration, in response to Lkn-l, was blocked by pertussis toxin (Ptx), a $G_o/G_i$ protein inhibitor, and U73122, a phospholipase C(PLC) inhibitor but not by protein kinase C inhibitor such as rottlerin, and Ro-31-8425. Taken together, our results demonstrate that Lkn-l transduces the chemotaxis signal through $G_o/G_i$ protein and PLC. This finding provides the molecular mechanism by which Lkn-l may contribute to neutrophil movement into the site of inflammation.

• BMB Reports
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• v.45 no.10
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• pp.583-588
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• 2012

Leukotactin(Lkn)-1 is a CC chemokine and is upregulated in macrophages in response to Mycobacterium tuberculosis (MTB) infection. We investigated whether mitogen-activated protein kinases (MAPKs) are involved in MTB-induced expression of Lkn-1. The up-regulation of Lkn-1 by infection with MTB was inhibited in cells treated with inhibitors specific for JNK (SP600125) or p38 MAPK (SB202190). Since the up-regulation of Lkn-1 by MTB has been reported to be mediated by the PI3-K/PDK1/Akt signaling, we examined whether JNK and/or p38 MAPK are also involved in this signal pathway. MTB-induced Akt phosphorylation was blocked by treatment with JNK- or p38 MAPK-specific inhibitors implying that p38 and JNK are upstream of Akt. In addition, treatment with the PI3-K-specific inhibitor inhibited MTB-stimulated activation of JNK or p38 MAPK implying that PI3-K is upstream of JNK and p38 MAPK. These results collectively suggest that JNK and p38 MAPK are involved in the signal pathway responsible for MTB-induced up-regulation of Lkn-1.

• 한국생물공학회:학술대회논문집
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• 2003.10a
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• pp.228-228
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• 2003

• Proceedings of the PSK Conference
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• 2002.04a
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• pp.152.2-152.2
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• 2002

• Nutrition Research and Practice
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• v.2 no.2
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• pp.134-137
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• 2008

Atherosclerosis is characterized by a chronic inflammatory disease, and chemokines play an important role in both initiation and progression of atherosclerosis development. Leukotactin-1 (Lkn-1/CCLl5), a new member of the human CC chemokine family, is a potent chemoattractant for leukocytes. Our previous study has demonstrated that Lkn-1/CCL15 plays a role in the initiation of atherosclerosis, however, little is currently known whether Lkn-1/CCL15 is associated with the progression of atherosclerosis. Matrix metalloproteinases (MMPs) in human coronary atherosclerotic lesions playa crucial role in the progression of atherosclerosis by altering the vulnerability of plaque rupture. In the present study, we examined whether Lkn-1/CCLl5 modulates MMP-9 release, which is a prevalent form expressed by activated macrophages and foam cells. Human THP-1 monocytic cells and/or human peripheral blood monocytes (PBMC) were treated with phorbol myristate acetate to induce their differentiation into macrophages. Foam cells were prepared by the treatment of THP-1 macrophages with human oxidized LDL. The macrophages and foam cells were treated with Lkn-1/CCL15, and the levels of MMP-9 release were measured by Gelatin Zymography. Lkn-1/CCL15 significantly enhanced the levels of MMP-9 protein secretion from THP-1 monocytic cells-derived macrophages, human PBMC-derived macrophages, as well as macrophage-derived foam cell in a dose dependent manner. Our data suggest that the action of Lkn-1/CCL15 on macrophages and foam cells to release MMP-9 may contribute to plaque destabilization in the progression of atherosclerosis.