To gain a better insight into the potential influence of tick SGE on the cell cytoskeleton, we used visualization of actin filaments. Specific staining of the actin cytoskeleton showed relatively minor differences in organization and design of actin filaments after treatment of cells with SGE prepared from female and male ticks in the early phase

of feeding and with male SGE fed for 7 days. By comparison, treatment with SGE prepared from females in the late feeding phase induced dramatic change in the integrity of the cell cytoskeleton, which was associated with loss of cell adhesion to the plate (Figure 7). Because the results obtained with H. excavatum SGE failed to support our previous observation that SGE-induced changes in cell morphology correlated with PDGF-binding activity, we screened with other cytokines. In the wound repair process, essential roles

are played by different types Metabolism inhibitor cancer of cytokines and growth factors, including keratinocyte growth factor (KGF/FGF7), interleukin 6 (IL-6) and the stromal cell-derived factor 1 (SDF-1/CXCL12). KGF and IL-6 are primarily produced in the mesenchyme and act on keratinocytes. Chemokine CXCL12 (SDF-1) is expressed in endothelial cells, myofibroblasts and keratinocytes. Its main HDAC inhibitor role is in the recruitment of lymphocytes to the wound, in the promotion of angiogenesis, although CXCL12 also enhances keratinocyte proliferation [16-18]. However, activity targeting IL-6, KGF and SDF-1α was not detected in any of the SGE preparations. The attachment and feeding of ixodid ticks involves penetration of their mouthparts into the host skin. The chelicerae, a pair of cutting digits that form part of the complex mouthparts, prepare the attachment site by scraping and digging into the skin. The hypostome is then inserted into the resulting cavity and is secured in the host skin by latex-like products of the salivary

glands that harden into a cement cone surrounding the hypostome. Skin injury caused by the attachment process should activate cells of the host immune system, the blood coagulation cascade and the inflammatory pathways. Cutaneous wound healing, the repair process after skin injury, requires interactions of different cell types, blood platelets, keratinocytes, fibroblasts, and epithelial, endothelial and immune cells. A complex healing process, involving migration of cells, interactions Molecular motor between cells, and interaction between cells and extracellular matrix, is provided and orchestrated by cytokines, chemokines and growth factors [19]. It is not easy to avoid reactions of the immune system, but ticks in their adaptation to their hosts have succeeded. In the fight with the host immune system, ticks employ molecules produced in, and secreted from, their salivary glands, which bind important cytokines. By this means, ticks are able to disrupt the chemical communication network between cells and to disorient immune cells in their patrolling job of immune surveillance [5, 6].