Potassium Channel-blockers as Therapeutic Agents to Interfere with Bone Resorption of Periodontal Disease

Abstract

AICD, activation-induced cell death; APC, antigen-presenting cells; B(K), large conductance; CRAC, calcium release-activated calcium channels; DC, dendritic cell; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; IFN-gamma, interferon-gamma; IP(3), inositol (1,4,5)-triphosphate; (K)ir, inward rectifier; JNK, c-Jun N-terminal kinase; I(K), intermediate conductance; LPS, lipopolysaccharide; L, ligand; MCSF, macrophage colony-stimulating factor; MHC, major histocompatibility complex; NFAT, nuclear factor of activated T-cells; RANK, receptor activator of nuclear factor-kappaB; T(CM), central memory T-cells; T(EM), effector memory T-cells; TNF, tumor necrosis factor; TRAIL, TNF-related apoptosis-inducing ligand; OPG, osteoprotegerin; Omp29, 29-kDa outer membrane protein; PKC, protein kinase C; PLC, phospholipase C; RT-PCR, reverse-transcriptase polymerase chain-reaction; S(K), small conductance; TCR, T-cell receptor; and (K)v, voltage-gated.

Cells move when ions and water flow

“…The ultimate question will of course be whether ion channel blockade can be exploited therapeutically in diseases that are associated with increased migratory activity such as inflammation and tumor metastases or in wound healing. The first promising results have been obtained [7, 38,79,110,131,143]. These studies also highlight the need for the development of new and more specific inhibitors.…”

B and T Lymphocytes Are the Primary Sources of RANKL in the Bone Resorptive Lesion of Periodontal Disease

“…We demonstrated that adoptive transfer of RANKL ϩ , antigen-specific T cells can induce bone loss in rat periodontal tissue that received local injection of the T-cell antigen. 17,18 Teng and colleagues 19 reported that adoptive transfer of an Actinobacillus actimomycetemcomitans-specific human T cell line isolated from patients with aggressive (juvenile) periodontal disease could induce significant periodontal bone loss in NOD/ SCID mice orally inoculated with A. actinomycetemcomitans every 3 days. 19 Although the latter report showed that systemic administration of OPG-Fc could reduce periodontal bone loss, it is not clear whether the transferred human T cells or bystander cells that might be secondarily stimulated by the transferred human T cells are the source of RANKL.…”

Voltage-gated Potassium Channel Modulation of Neurotoxic Activity in Human Immunodeficiency Virus Type-1(HIV-1)-Infected Macrophages

“…Current approaches to treat the neurodegenerative disorders include immunomodulatory therapy to treat neuroinflammation and possibly limit neurodegeneration, in conjunction with symptomatic treatment of neurological deficits . As a key signal for such macrophage function as cytotoxin production, in addition to physiological functions such as proliferation and differentiation, Kv channels have become the potential targets for the development of therapeutic strategies for central nervous system inflammation and degeneration and other diseases (Valverde et al 2005). To date, two relative nonspecific Kv channel blockers 4-AP and 3,4-diaminopyridine (3,4-DAP) have been tested clinically for their efficacy in the treatment of patients with MS (Bever et al 1990(Bever et al , 1994.…”