Fusobacterium nucleatum induces cytokine production through Toll-like-receptor-independent mechanism

• AimTo determine whether Fusobacterium nucleatum's ability to invade cells allows the bacteria to activate pro-inflammatory response through cytosolic pattern recognition receptors, independent of surface Toll-like receptors (TLRs). MethodologyHEK293T cells, which lack endogenous TLRs, and overexpressing dominant negative myeloid differentiation primary response gene 88 (MyD88DN) protein, were infected with F.nucleatum and the production of interleukin-8 (IL-8) was determined. The necessity for intracellular invasion of the bacteria for cytokine production was also investigated by blocking bacterial invasion with cytochalasin D. The roles of NF?B and p38 mitogen-activated protein kinase (MAPK) and nucleotide-binding oligomerization domain-1 (NOD-1) signalling pathways in F.nucleatum-induced IL-8 secretion were determined. ResultsFusobacterium nucleatum-infected HEK293T cells produced IL-8 independent of the MYD88 signalling. This response was inhibited by preventing F.nucleatum invasion into HEK293T cells. p38 MAPK but not the NF?B signalling pathway was required for F.nucleatum-mediated IL-8 production. HEK293T cells expressed NOD-1 but not NOD-2. Yet, inhibition of NOD-1 signalling did not affect F.nucleatum-induced IL-8 secretion. ConclusionsFusobacterium nucleatum invasion led to cytokine production, which is mediated by the p38 MAPK signalling but independent of TLRs, NOD-1, NOD-2 and NF?B signalling.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Odontologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Dentistry (hsv//eng)

Nyckelord

bacterial invasion

Fusobacterium nucleatum

nucleotide-binding oligomerization domain-1

PRIMARY ENDODONTIC INFECTIONS

ORAL EPITHELIAL-CELLS

DENTAL-PULP

KAPPA-B

PERIAPICAL LESIONS

EXPRESSION

BACTERIA

TEETH

INTERLEUKIN-8

INFLAMMATION

Dentistry

Oral Surgery & Medicine

DENTISTRY

ORAL SURGERY & MEDICINE

VELOPMENTAL EVOLUTION

V312B

P425

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