THE H. PYLORI-RELATED VIRULENCE FACTOR CAGA INFLUENCES THE EXPRESSION OF CHEMOKINES CXCL10, CCL17, CCL20, CCL22, AND THEIR RECEPTORS BY PERIPHERAL BLOOD MONONUCLEAR CELLS FROM PEPTIC ULCER PATIENTS

O fator de virulência relacionado ao H. pylori influencia a expressão de quimiocinas CXCL10, CCL17, CCL20, CCL22, e seus receptores por células mononucleares de sangue periféricos de pacientes com úlceras pépticas

ABSTRACT

BACKGROUND:

During the Helicobacter pylori (HP) infection, the infiltration of the leukocytes into stomach mucosa is directed by locally produced chemokines that play a decisive role in infection outcome. The CagA is the most potent virulence factor of HP, so that the infection with CagA ⁺ strains is associated with more severe complications than infection with CagA ^- HP.

OBJECTIVE:

The aim was to determine the expression of chemokines CXCL10, CCL17, CCL20 and CCL22, and their receptors by CagA ⁺ HP- and CagA ^- HP-derived crude extract (HP-CE)-stimulated peripheral blood mononuclear cells (PBMCs) from peptic ulcer (PU) patients.

METHODS:

The serum and the PBMCs were collected from 20 HP-infected PU patients, 20 HP-infected asymptomatic subjects (HIA) and 20 non-infected healthy subjects (NHS). The PBMCs were cultured in absence of stimulator or with 10 µg CagA ⁺ HP crude extract (CagA ⁺ CE), 10 µg CagA ^- HP crude extract (CagA ^- CE). Chemokines and receptors were measured by ELISA and real time-PCR respectively.

RESULTS:

In PU patients, the production of chemokines CXCL10, CCL17, CCL20 and CCL22, and the expression of chemokine receptors CXCR3, CCR4 and CCR6 by CagA ⁺ CE-induced PBMCs were significantly higher than non-stimulated and CagA ^- CE stimulated cultures. The CXCL10 production by CagA ⁺ CE stimulated PBMCs from HIA subjects was significantly higher than the equal cultures from PU and NHS groups. The CCL17 and the CCL20 production by non-stimulated, CagA ⁺ CE stimulated, and CagA ^- CE stimulated PBMCs from PU subjects were significantly higher than the equal cultures from NHS and HIA groups. The CCL22 production by non-stimulated, CagA ⁺ CE stimulated and CagA ^- CE stimulated PBMCs from NHS group were significantly higher than the equal cultures from HIA and PU groups. The CagA ⁺ CE stimulated PBMCs from HIA subjects expressed lower amounts of CCR6 in comparison with CagA ⁺ CE stimulated PBMCs from NHS and PU groups. The serum levels CXCL10 and CCL20 in PU and HIA groups were significantly higher than NHS subjects. NHS and HIA groups displayed higher serum levels of CCL22 in comparison with PU patients.

CONCLUSION:

Results indicated that the CagA status of bacterium influence the expression of chemokines and receptors by HP-CE stimulated PBMCs from PU patients.

HEADINGS:
Helicobacter pylori; CagA; Chemokines; Chemokine receptors; Peptic ulcer