Patterns of chemokines and chemokine receptors expression in different forms of human periodontal disease

Abstract

Current knowledge states that periodontal diseases are chronic inflammatory reactions raised in response to periodontopathogens. Many cell types and mediators, including Th1 and Th2 lymphocytes, cytokines and chemokines, appear to be involved in the immunopathogenesis of periodontal diseases. Chemokines, a family of chemotactic cytokines, bind to specific receptors and selectively attract different cell subsets to the inflammatory site. They can also interact with classical cytokines and modulate the local immune response. In order to study the role of chemokines in periodontal diseases, we examined the expression of chemokines, chemokine receptors and cytokines by means of reverse transcription-polymerase chain reaction (RT-PCR) techniques. Characteristic patterns of such factors' expression were found in gingival biopsies from patients presenting with aggressive periodontitis and chronic periodontitis. The expression of the chemokines macrophage inflammatory protein-1 alpha (MIP-1alpha) and interferon-gamma inducible protein 10 (IP-10) and of their respective receptors, CCR5 and CXCR3, were more prevalent and higher in aggressive periodontitis, and associated with higher interferon-gamma (IFN-gamma) expression and lower interleukin-10 (IL-10) expression. In contrast, chronic periodontitis patients exhibited a more frequent and higher expression of monocyte chemoattractant protein-1 (MCP-1) and its receptor CCR4, and higher expression of IL-10. It is possible that chemokines, in addition to the classical cytokines, are involved in the immunopathogenesis of periodontal disease, driving the migration and the maintenance of several inflammatory cell types such as polymorphonuclear leukocytes, dendritic cells (DCs), natural killer cells, macrophages, and subsets of lymphocytes in the gingival tissues. These cells are thought to participate in the inflammatory and immune reaction that takes place in periodontal disease, killing pathogens, presenting antigens, and producing cytokines. The selective recruitment of polarized lymphocyte subsets could result in differential cytokine production at the site of response, which is supposed to determine the stable or progressive nature of the lesion. Besides, the role of chemokines as activators and chemoattracts of osteclasts may be involved in the determination of disease severity.

Anti-Inflammatory Cytokines in Peri-Implant Soft Tissues: A Preliminary Study on Humans Using CDNA Microarray Technology

“…However, the development of a predominantly Th2 response was related to chronic periodontitis, while a Th 1response was thought to be involved in aggressive periodontitis (30). Considering these recent findings, it is difficult to interpret some of our results.…”

The Role of Chemokines and Cytokines in the Pathogenesis of Periodontal and Periapical Lesions: Current Concepts

“…Regulated upon Activation Normal T-cell Expressed and Secreted (RANTES/CCL5) is found in greater levels in active periodontal lesions compared to inactive sites (Gamonal et al, 2001, Gemmell et al, 2001) and it chemoattracts lymphocytes and monocytes as well as other cell types (Koch et al, 2005, Schall et al, 1990. The involvement of CCL5 in periodontal bone resorption is supported by findings that it binds to CCR1 and/or CCR5 (Garlet et al, 2003), inducing chemotaxis and the formation of osteoclasts in vitro (Yu et al, 2004). Fibroblasts from patients with rheumatoid arthritis, which shares some inflammatory features with PD, produce CCL5 mRNA upon stimulation with TNF-, IL-1, or IFN- (Koch et al, 2005, Volin et al, 1998 and this production of CCL5 can participate in cytokine networks by inducing the production of CXCL8 and IL-6 (Nanki et al, 2001).…”

“…IFN- is the signature cytokine of Th1-type responses, being considered the main phagocyteactivating cytokine and characteristically associated with the production of inflammatory cytokines and chemokines (Appay et al, 2008, Murphy & Reiner, 2002, Sallusto & Lanzavecchia, 2011, Schroder et al, 2004. Concerning periapical diseases of endodontic origin and periodontitis, IFN- is present at high levels in chronic PLs, and is associated with progressive lesions or higher severity (Colic et al, 2006, Garlet et al, 2003, Honda et al, 2006. In agreement, studies in rodents demonstrated that IFN- is involved in the development of inflammatory reaction and bone resorption in response to A. actinomycetemcomitans and P. gingivalis (Baker et al, 1999, Teng et al, 2005.…”

Immunological Profiles in HIV Positive Patients with or without Opportunistic Infections and the Influence of Highly Active Antiretroviral Therapy: A Systematic Review and Update

“…For instance, elevated levels of this chemokine have been reported in different viral infections such as severe influenza infection [2,87], West Nile virus infection [88], acute and chronic Hepatitis C [89], showcasing its involvement in immune responses during viral infections. However, during HIV mono-infection, levels of IP-10 are upregulated compared to healthy individuals [35,90,91].…”