Absence of exogenous interleukin-4-induced apoptosis of gingival macrophages may contribute to chronic inflammation in periodontal diseases.
Inflamed gingival tissues are enriched in macrophages (MOs) and CD4-positive T cells; however, T helper-type cytokines such as interleukin (IL)-2 and IL-4 are absent. Therefore, we investigated whether a relationship exists between IL-4 receptor (IL-4R) expression and MO persistence in the absence of exogenous IL-4. Gingival MOs, when compared with monocyte(MN)/MOs from peripheral blood mononuclear cells, expressed high levels of IL-4R mRNA. Furthermore, in vitro cultures of gingival MOs remained viable whereas identically treated peripheral blood MN/MOs rapidly lost viability. However, when gingival MOs were incubated with recombinant IL-4 (rIL-4), the cell viability was dramatically reduced. When the frequency of apoptotic cells was assessed in rIL-4-treated gingival MO cultures, higher numbers of apoptotic cells were noted in rIL-4-treated versus control cultures. Furthermore, rIL-4-treated MOs from inflamed gingiva showed DNA fragmentation as assessed by electrophoresis. These findings clearly show that addition of exogenous rIL-4 to gingival MO cultures leads to cell death by apoptosis. This finding would suggest that topical application of rIL-4 may inhibit the persistence of MOs in adult periodontitis, which could then lead to decreased inflammation.
Department of Oral Biology, University of Alabama at Birmingham Medical Center 35294-2170, USA.
M
M
Yamamoto
K
K
Kawabata
K
K
Fujihashi
J R
JR
McGhee
T E
TE
Van Dyke
T V
TV
Bamberg
T
T
Hiroi
H
H
Kiyono
D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis; D001483:Base Sequence; D004249:DNA Damage; D005881:Gingiva / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008969:Molecular Sequence Data; D010510:Periodontal Diseases / Q000276:immunology / Q000503:physiopathology*; D016133:Polymerase Chain Reaction; D018123:Receptors, Interleukin / Q000378:metabolism; D019948:Receptors, Interleukin-4; D013997:Time Factors
D015703:Antigens, CD; D018123:Receptors, Interleukin; D019948:Receptors, Interleukin-4; D015847:Interleukin-4